ArticleLiterature Review

The neural basis of drug craving: An incentive-sensitization theory of addiction

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Abstract

This paper presents a biopsychological theory of drug addiction, the 'Incentive-Sensitization Theory'. The theory addresses three fundamental questions. The first is: why do addicts crave drugs? That is, what is the psychological and neurobiological basis of drug craving? The second is: why does drug craving persist even after long periods of abstinence? The third is whether 'wanting' drugs (drug craving) is attributable to 'liking' drugs (to the subjective pleasurable effects of drugs)? The theory posits the following. (1) Addictive drugs share the ability to enhance mesotelencephalic dopamine neurotransmission. (2) One psychological function of this neural system is to attribute 'incentive salience' to the perception and mental representation of events associated with activation of the system. Incentive salience is a psychological process that transforms the perception of stimuli, imbuing them with salience, making them attractive, 'wanted', incentive stimuli. (3) In some individuals the repeated use of addictive drugs produces incremental neuroadaptations in this neural system, rendering it increasingly and perhaps permanently, hypersensitive ('sensitized') to drugs and drug-associated stimuli. The sensitization of dopamine systems is gated by associative learning, which causes excessive incentive salience to be attributed to the act of drug taking and to stimuli associated with drug taking. It is specifically the sensitization of incentive salience, therefore, that transforms ordinary 'wanting' into excessive drug craving. (4) It is further proposed that sensitization of the neural systems responsible for incentive salience ('for wanting') can occur independently of changes in neural systems that mediate the subjective pleasurable effects of drugs (drug 'liking') and of neural systems that mediate withdrawal. Thus, sensitization of incentive salience can produce addictive behavior (compulsive drug seeking and drug taking) even if the expectation of drug pleasure or the aversive properties of withdrawal are diminished and even in the face of strong disincentives, including the loss of reputation, job, home and family. We review evidence for this view of addiction and discuss its implications for understanding the psychology and neurobiology of addiction.

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... According to this model, Individuals who are more impulsive when negative affect is elevated could acquire the expectancy that impulsive actions such as BE alleviate negative affect. Separately, the incentive sensitization theory suggests that repeated BE episodes are themselves a maintaining factor for BE (Robinson & Berridge, 1993). This is because they are thought to sensitize the reward system to the anticipation of food, leading to a higher incentive salience (i.e., "wanting") (Robinson & Berridge, 1993). ...
... Separately, the incentive sensitization theory suggests that repeated BE episodes are themselves a maintaining factor for BE (Robinson & Berridge, 1993). This is because they are thought to sensitize the reward system to the anticipation of food, leading to a higher incentive salience (i.e., "wanting") (Robinson & Berridge, 1993). However, repeated BE episodes could also cause habituation of the reward system to receiving food, leading to a lower responsivity and necessitating the consumption of even larger amounts to elicit the same response (Berridge & Robinson, 2016). ...
... The findings concerning the anticipation and receipt of highenergy-density food are in line with the incentive-sensitization theory of BE. This theory hypothesizes that repeated BE episodes sensitize the brain to food and that this leads to a higher incentive salience (i.e., wanting) for food (Robinson & Berridge, 1993). This sensitization of the brain could be the reason why a higher activity of the ACC, insula, and mOFC is seen during the anticipation of high-energy-density food, but not money. ...
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Objective: Changes in reward processing are hypothesized to play a role in the onset and maintenance of binge eating (BE). However, despite an increasing number of studies investigating the neurobiological reward system in individuals who binge eat, no comprehensive systematic review exists on this topic. Therefore, this review has the following objectives: (1) identify structural and functional changes in the brain reward system, either during rest or while performing a task; and (2) formulate directions for future research. Methods: A search was conducted of articles published until March 31, 2022. Neuroimaging studies were eligible if they wanted to study the reward system and included a group of individuals who binge eat together with a comparator group. Their results were summarized in a narrative synthesis. Results: A total of 58 articles were included. At rest, individuals who binge eat displayed a lower striatal dopamine release, a change in the volume of the striatum, frontal cortex, and insula, as well as a lower frontostriatal connectivity. While performing a task, there was a higher activity of the brain reward system when anticipating or receiving food, more model-free reinforcement learning, and more habitual behavior. Most studies only included one patient group, used general reward-related measures, and did not evaluate the impact of comorbidities, illness duration, race, or sex. Discussion: Confirming previous hypotheses, this review finds structural and functional changes in the neurobiological reward system in BE. Future studies should compare disorders, use measures that are specific to BE, and investigate the impact of confounding factors. Public significance statement: This systematic review finds that individuals who binge eat display structural and functional changes in the brain reward system. These changes could be related to a higher sensitivity to food, relying more on previous experiences when making decisions, and more habitual behavior. Future studies should use a task that is specific to binge eating, look across different patient groups, and investigate the impact of comorbidities, illness duration, race, and sex.
... According to the incentive-sensitization theory, environmental cues associated with the experience of drug consumption can have a strong motivational impact on cue-triggered wanting of a drug reward [14][15][16]. A stronger wanting of the drug itself -in contrast to liking -has been shown in addicted animals and in human studies with patients suffering from addiction [17]. ...
... Sebold et al. [36] further investigated potential biomarkers for the wanting of drug-related cues according to the incentive-sensitization theory [14]. They investigated the A118G polymorphism of the OPRM1 gene, money-related PIT, and relapse rates in recently detoxified AD patients, as well as two independent HC samples. ...
... Over-eating, as a major cause of obesity, may be wellexplained by the excessive wanting as proposed within the incentive-sensitization theory for addictions mentioned above [14]. Once highly palatable food becomes excessively wanted, it could be highly attention-grabbing and lead to overconsumption [15]. ...
Article
A mechanism known as Pavlovian-to-instrumental transfer (PIT) describes a phenomenon by which the values of environmental cues acquired through Pavlovian conditioning can motivate instrumental behavior. PIT may be one basic mechanism of action control that can characterize mental disorders on a dimensional level beyond current classification systems. Therefore, we review human PIT studies investigating subclinical and clinical mental syndromes. The literature prevails an inhomogeneous picture concerning PIT. While enhanced PIT effects seem to be present in non-substance-related disorders, overweight people, and most studies with AUD patients, no altered PIT effects were reported in tobacco use disorder and obesity. Regarding AUD and relapsing alcohol-dependent patients, there is mixed evidence of enhanced or no PIT effects. Additionally, there is evidence for aberrant corticostriatal activation and genetic risk, e.g., in association with high-risk alcohol consumption and relapse after alcohol detoxification. In patients with anorexia nervosa, stronger PIT effects elicited by low caloric stimuli were associated with increased disease severity. In patients with depression, enhanced aversive PIT effects and a loss of action-specificity associated with poorer treatment outcomes were reported. Schizophrenic patients showed disrupted specific but intact general PIT effects. Patients with chronic back pain showed reduced PIT effects. We provide possible reasons to understand heterogeneity in PIT effects within and across mental disorders. Further, we strengthen the importance of reliable experimental tasks and provide test-retest data of a PIT task showing moderate to good reliability. Finally, we point toward stress as a possible underlying factor that may explain stronger PIT effects in mental disorders, as there is some evidence that stress per se interacts with the impact of environmental cues on behavior by selectively increasing cue-triggered wanting. To conclude, we discuss the results of the literature review in the light of Research Domain Criteria, suggesting future studies that comprehensively assess PIT across psychopathological dimensions.
... The findings indicated that the valence of the cues was not aiding the maintenance of the behaviour, i.e. that motivation to maintain self-harming persisted regardless of the attribution of the cues, refuting predictions made by OPT. The final set of studies used an implicit task to test predictions made by another addiction theory (the Incentive Sensitisation Theory; Robinson & Berridge, 1993). An attentional bias toward words associated with self-harm and personalised self-harm picture stimuli was demonstrated by those currently self-harming but not by those who had never self-harmed, supporting predictions made by the theory; however abstainers also demonstrated a lack of attentional vigilance to self-harm cues, refuting predictions made by IST. ...
... There are many reports of addicts increasing their drug consumption over time (F alk et aI., 1983). Increased dosage with experience has been attributed to an 25 Chapter One overall reduction in affective response (Solomon, 1980) or tolerance to aversive effects (Robinson & Berridge, 1993). Those who abuse drugs report that they experience increasing urges to do so and that it becomes increasingly difficult for them to control the behaviour. ...
... Moreover, prolonged selfharming, like prolonged drug addiction, has many negative consequences, such as stigma, scatTing, loss of income and breakdown in relationships (Smith et aI., 1988). Robinson and Berridge (1993) argue that such consequences often far outweigh the magnitude of (drug) pleasure or the memory of (drug) pleasure. The same argument can be applied to any account of addiction, since continued use despite negative consequences is a central component of the concept. ...
Thesis
p>This thesis focuses on two prominent theories of addiction and the predictions that they make when applied to DSH. Results from the second study indicated that those who self-harm endorse many criteria of clinical dependence and behavioural addiction. The results also suggested that theories of addiction may go some way towards enhancing our understanding of the mechanisms that maintain DSH. Reported pain was significantly higher for early self-harming episodes compared to later episodes and accidental episodes and accidental episodes of injury. Longer lasting tension effects were reported for later episodes. Episodes of DSH also regulated the intensity of happiness, anger and sadness. This supports predictions made by the Opponent Process theory (OPT) of addiction. However, OPT could not account for all of the results. Emotional regulation was not more pronounced in later episodes, neither were injuries more severe. Further testing of this theory was therefore necessary. The third study considered the valence of cues associated with self-harm, using implicit and explicit measures. The findings indicate that the valence of the cues was not aiding the maintenance of the behaviour, i.e. that motivation to maintain self-harming persisted regardless of the attribution of the cues, refuting predictions made by OPT. The final set of studies used an implicit task to test predictions made by another addiction theory (the Incentive Sensitisation Theory; Robinson & Berridge, 1993). An attentional bias toward words associated with self-harm and personalised self-harm picture stimuli was demonstrated by those currently self-harming but not by those who had never self-harmed, supporting predictions made by the theory; however abstainers also demonstrated a lack of attentional vigilance to self-harm cues, refuting predictions made by IST.</p
... Sensitization is an enhancement in the ability of a drug of abuse to activate DA neurotransmission, increase locomotor activation, and support self-administration following previous drug exposure. Sensitization is thought to play a major role in the long-lasting maintenance of drug use and the reinstatement of drug-seeking behaviors (Kawa et al. 2019;Robinson and Berridge 1993;Vanderschuren and Kalivas 2000;Vezina 2004;Wolf 1998). Changes in ventral tegmental area (VTA) glutamatergic signaling, whereby glutamatergic excitation of VTA DA neurons is strengthened following drug exposure, have long been implicated in the behavioral changes that result from repeated drug exposure and are thought to be critical for the development of sensitization (Argilli et al. 2008;Borgland et al. 2004;Carlezon and Nestler 2002;Churchill et al. 1999;Fitzgerald et al. 1996;Saal et al. 2003;Ungless et al. 2001;White et al. 1995;Zhang et al. 1997). ...
... We show that halorhodopsin-mediated inhibition of GLU signaling in either the LDTg or the VTA during cocaine exposure prevented the induction of sensitization by cocaine as evidenced by the absence of enhanced locomotor responding on the subsequent test. Similar findings were obtained with sensitization of NAcc DA overflow, which has long been hypothesized to underlie the enhanced craving and higher propensity to relapse associated with drug abuse (Kalivas et al. 1998;Robinson and Berridge 1993). Our results identify LDTg GLU inputs to the VTA as critical for the development of locomotor and NAcc DA sensitization by cocaine. ...
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RationaleDrug-induced potentiation of ventral tegmental area (VTA) glutamate signaling contributes critically to the induction of sensitization - an enhancement in responding to a drug following exposure which is thought to reflect neural changes underlying drug addiction. The laterodorsal tegmental nucleus (LDTg) provides one of several sources of glutamate input to the VTA.Objective We used optogenetic techniques to test either the role of LDTg glutamate cells or their VTA afferents in the development of cocaine sensitization in male VGluT2::Cre mice. These were inhibited using halorhodopsin during each of five daily cocaine exposure injections. The expression of locomotor sensitization was assessed following a cocaine challenge injection 1-week later.ResultsThe locomotor sensitization seen in control mice was absent in male mice subjected to inhibition of LDTg-VTA glutamatergic circuitry during cocaine exposure. As sensitization of nucleus accumbens (NAcc) dopamine (DA) overflow is also induced by this drug exposure regimen, we used microdialysis to measure NAcc DA overflow on the test for sensitization. Consistent with the locomotor sensitization results, inhibition of LDTg glutamate afferents to the VTA during cocaine exposure prevented the sensitization of NAcc DA overflow observed in control mice.Conclusions These data identify the LDTg as the source of VTA glutamate critical for the development of cocaine sensitization in male mice. Accordingly, the LDTg may give rise to the synapses in the VTA at which glutamatergic plasticity, known to contribute to the enhancement of addictive behaviors, occurs.
... In humans, we defined cognition as any construct that typically falls within the umbrella of neuropsychological testing, as well as brain-based studies. We also included more distal constructs of cognition, like craving and impulsivity, because they play a prominent role in addictive behaviors [35,36]. In rodents, we defined cognition as attention, learning, and memory in line with a seminal review paper [37]. ...
... Furthermore, because many rodent studies assessed anxiety-related behaviors and the high degree of comorbidity between anxiety disorders and alcohol addiction [40], we also included anxiety as a secondary outcome. On the other hand, locomotor activity was excluded as an outcome because even though behavioral sensitization is considered to reflect neurobiological changes that may underlie certain aspects of addictive behavior [36], the translational relevance for addictive behavior and human addiction in particular remains unclear [41,42]. Across both rodents and humans, general alcohol metabolization and ethanol withdrawal studies were not included except if they included brain-related outcomes. ...
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Adolescence is an important developmental period associated with increased risk for excessive alcohol use, but also high rates of recovery from alcohol use-related problems, suggesting potential resilience to long-term effects compared to adults. The aim of this systematic review is to evaluate the current evidence for a moderating role of age on the impact of chronic alcohol exposure on the brain and cognition. We searched Medline, PsycInfo, and Cochrane Library databases up to February 3, 2021. All human and animal studies that directly tested whether the relationship between chronic alcohol exposure and neurocognitive outcomes differs between adolescents and adults were included. Study characteristics and results of age-related analyses were extracted into reference tables and results were separately narratively synthesized for each cognitive and brain-related outcome. The evidence strength for age-related differences varies across outcomes. Human evidence is largely missing, but animal research provides limited but consistent evidence of heightened adolescent sensitivity to chronic alcohol’s effects on several outcomes, including conditioned aversion, dopaminergic transmission in reward-related regions, neurodegeneration, and neurogenesis. At the same time, there is limited evidence for adolescent resilience to chronic alcohol-induced impairments in the domain of cognitive flexibility, warranting future studies investigating the potential mechanisms underlying adolescent risk and resilience to the effects of alcohol. The available evidence from mostly animal studies indicates adolescents are both more vulnerable and potentially more resilient to chronic alcohol effects on specific brain and cognitive outcomes. More human research directly comparing adolescents and adults is needed despite the methodological constraints. Parallel translational animal models can aid in the causal interpretation of observed effects. To improve their translational value, future animal studies should aim to use voluntary self-administration paradigms and incorporate individual differences and environmental context to better model human drinking behavior.
... The ability of sexual reward to induce CPP, CEP, partner preference, and to enhance appetitive sexual behaviors, must involve a process of sensitized attention to environmental and partner-related cues. One of the classic mechanisms of attention to reward-related cues is the sensitized activation of mesolimbic/mesocortical DA [150][151][152][153][154] (see Figure 5). The A10 DA neurons that make up this pathway originate in the ventromedial portion of the VTA and project to a number of cortical and limbic sites, including the prefrontal cortex, anterior cingulate, septum, amygdala, and NAc [155][156][157]. ...
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Although mechanisms of mate preference are thought to be relatively hard-wired, experience with appetitive and consummatory sexual reward has been shown to condition preferences for partner related cues and even objects that predict sexual reward. Here, we reviewed evidence from laboratory species and humans on sexually conditioned place, partner, and ejaculatory preferences in males and females, as well as the neurochemical, molecular, and epigenetic mechanisms putatively responsible. From a comprehensive review of the available data, we concluded that opioid transmission at μ opioid receptors forms the basis of sexual pleasure and reward, which then sensitizes dopamine, oxytocin, and vasopressin systems responsible for attention, arousal, and bonding, leading to cortical activation that creates awareness of attraction and desire. First experiences with sexual reward states follow a pattern of sexual imprinting, during which partner- and/or object-related cues become crystallized by conditioning into idiosyncratic “types” that are found sexually attractive and arousing. These mechanisms tie reward and reproduction together, blending proximate and ultimate causality in the maintenance of variability within a species.
... In addition, CBD promotes protection against the harmful effects of alcohol on the liver and brain and reduces oxidative stress (Nona et al. 2019;Yang et al. 2014;Consroe et al. 1979). On the other hand, this interaction promoted motor and psychomotor disruptions (Robinson and Berridge 1993). Thus, as discussed, further double-blind, controlled, randomized studies are essential to assess the interactions of CBD with other drugs, as well as bioavailability, pharmacokinetics, and pharmacodynamics assessments in these contexts. ...
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Rationale Autism spectrum disorder (ASD) is defined as a group of neurodevelopmental disorders whose symptoms include impaired communication and social interaction, restricted and repetitive patterns of behavior, and varying levels of intellectual disability. ASD is observed in early childhood and is one of the most severe chronic childhood disorders in prevalence, morbidity, and impact on society. It is usually accompanied by attention deficit hyperactivity disorder, anxiety, depression, sleep disorders, and epilepsy. The treatment of ASD has low efficacy, possibly because it has a heterogeneous nature, and its neurobiological basis is not clearly understood. Drugs such as risperidone and aripiprazole are the only two drugs available that are recognized by the Food and Drug Administration, primarily for treating the behavioral symptoms of this disorder. These drugs have limited efficacy and a high potential for inducing undesirable effects, compromising treatment adherence. Therefore, there is great interest in exploring the endocannabinoid system, which modulates the activity of other neurotransmitters, has actions in social behavior and seems to be altered in patients with ASD. Thus, cannabidiol (CBD) emerges as a possible strategy for treating ASD symptoms since it has relevant pharmacological actions on the endocannabinoid system and shows promising results in studies related to disorders in the central nervous system. Objectives Review the preclinical and clinical data supporting CBD’s potential as a treatment for the symptoms and comorbidities associated with ASD, as well as discuss and provide information with the purpose of not trivializing the use of this drug.
... It has also been suggested that the prefronto-accumbal glutamatergic pathway contributes to the mediation of reward [63]. Furthermore, glutaminergic transmission is heavily involved in sensitisation; the associated increase in incentive salience with repeated drug-taking [64]. This is evident through changes in glutaminergic transmission that occur in response to sensitizing treatment schedules of drugs of abuse, likely through activation of D 1 receptors which augments glutaminergic activity through increased expression of NMDA receptors post-synaptically [65]. ...
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We are amidst a global addiction crisis, yet stigmas surrounding addiction counterintuitively prevail. Understanding and appreciating the neurobiology of addiction is essential to dissolve this stigma and for the development of new pharmacological agents to improve upon currently narrow therapeutic options. This review highlights this and evaluates dopamine-and-cAMP-regulated phosphoprotein, Mr 32 kDa (DARPP-32) as a potential target to treat various forms of substance abuse. Despite the proven involvement of DARPP-32 in addiction pathophysiology, no robust investigations into compounds that could pharmacologically modulate it have been carried out. Agents capable of altering DARPP-32 signalling in this way could prevent or reverse drug abuse and improve upon currently substandard treatment options.
... Drugrelated cues are also key factors in drug use and relapse after treatment (Tiffany, 1990). Incentive sensitization theory indicates that drug-related stimuli will selectively attract the attention of individuals with SUD (Robinson & Berridge, 1993). Attentional bias towards addictive information stimuli is one of the reasons that lead to drug seeking and relapse behavior (Field & Cox, 2008). ...
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Individuals with substance use disorder (SUD) tend to have attention bias to drug and negative emotions, which leads to drug craving and relapse. This study examines attentional bias from the time dimension, and adopts the rapid sequence visual presentation (RSVP) paradigm to study the attentional blink effect of individuals with SUD towards different types of negative words. A total of 55 males with SUD were recruited from a compulsory drug rehabilitation center in Jiangxi Province. The results indicated that the following: (1) The accuracy of T2 recognition when T1 was correctly recognized (T2|T1) increased with the increase of the time interval, indicating that the attentional blink was successfully induced. (2) When T1 was addictive vocabulary, compared with the neutral vocabulary, the attentional blink effect of males with SUD was enhanced. When T2 was negative addiction vocabulary or negative vocabulary, compared with the neutral vocabulary, the attentional blink of males with SUD was weakened. The current research results not only find that males with SUD have an attention bias towards addiction clues from the time characteristics of the attention process, but also it is of great significance to guide the rehabilitation centers to improve the craving and relapse of males with SUD by reducing the appearance of negative addictive information.
... Such disruptions include the impact of natural reinforcers and drugs of abuse that stimulate the same substrates at supraphysiological levels of intensity. Behavioral, cognitive, affective, and physiological reactions are mediated by opioid and dopaminergic systems that involve the ventral striatum and produce hedonic 'liking', as well as mesolimbic projections that generate motivationally potent 'wanting' and habit formation (Robinson & Berridge, 1993). The net response to an acute exposure is determined by activation of hedonic and other modulatory systems, plus the action of compensatory 'opponent processes' that dampen those effects to minimize chronic homeostatic disruption (Solomon & Corbit, 1974). ...
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It is not known why some novice gamblers eventually develop Gambling Disorder while most do not. This study tested predictions from two competing models of Gambling Disorder etiology: the Pathways Model of Problem and Pathological Gambling (Blaszczynski & Nower, 2002) and the Allostatic Model of addictions (Koob & Schulkin, 2019) applied to Gambling Disorder. Participants were drawn from introductory psychology courses and screened as non-gamblers (N = 91). They completed computerized versions of the Iowa Gambling Task (IGT-2), Wisconsin Sorting Task (WCST-64), and a Difficulties with Emotional Regulation Scale (DERS). Risk-taking tendencies were observed by having participants play a typical electronic slots game for up to 15 min. Higher betting on the slots game was correlated with the frequency of Deck A selections on the IGT-2 and lower total DERS scores. There were no significant correlations involving slots betting and the WCST-64. Greater risk-taking on the slots game was correlated with more frequent wins, partial losses that were disguised as wins, bonus game features, and the largest nominal amount won on a single spin. However, there were no significant correlations between betting behaviors and the ‘payback percentage’, defined as total winnings as a proportion of total wagers made throughout the session. Post-game ratings were positively correlated with frequency of reinforcing outcomes. These findings suggest that novice gamblers’ likelihood of further gambling participation may be elevated by high sensitivity to immediate rewards and low difficulty self-regulating negative emotions. These findings are consistent with the Allostatic Model; they are not consistent with Pathways Model.
... Prior studies have argued that the different levels of the NE system might mediate arousal states 53,54 . However, other studies refine the understanding of the LC-NE function by relating it with optimization of reward-seeking behavior 30 . ...
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In the context of visual attention, it has been classically assumed that missing the response to a target or erroneously selecting a distractor occurs as a consequence of the (miss)allocation of attention in space. In the present paper, we challenge this view and provide evidence that, in addition to encoding spatial attention, prefrontal neurons also encode a distractibility-to-impulsivity state. Using supervised dimensionality reduction techniques in prefrontal neuronal recordings in monkeys, we identify two partially overlapping neuronal subpopulations associated either with the focus of attention or overt behaviour. The degree of overlap accounts for the behavioral gain associated with the good allocation of attention. We further describe the neural variability accounting for distractibility-to-impulsivity behaviour by a two dimensional state associated with optimality in task and responsiveness. Overall, we thus show that behavioral performance arises from the integration of task-specific neuronal processes and pre-existing neuronal states describing task-independent behavioral states.
... We inferred from the results that, although two disorders ended up affecting similar circuits, abnormalities in ADHD may initially originate from immature frontal cortices and progress into regions governing motor control and the reward system, which is a form of top-down regulation [89]. In contrast, the neuropathological processing underlying SUDs could be triggered by drug-related adaptations in neural systems, mainly a hyperactive reward system, which initially occurs in the striatum [9,90]. Impelled by up-regulated motivation, cravings, and reinforcing effects of drugs, damage with continuous substance administration extends to prefrontal circuits, leading to impaired executive function [91][92][93]. ...
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As two common mental disorders during the period of adolescence that extend to early adulthood, attention-deficit/hyperactivity disorder (ADHD) and substance use disorders (SUDs) have considerable diagnostic co-occurrence and shared neuropsychological impairments. Our study aimed to identify overlapping and distinct brain structural abnormalities associated with ADHD and SUDs among adolescents and young adults. A systematic literature search on voxel-based morphometry (VBM) studies of ADHD and SUDs was conducted in PubMed and Web of Science. Data were extracted and analyzed to identify brain abnormalities using Seed-based d-Mapping software. Data-driven functional decoding was conducted to identify the psychophysiological functioning associated with brain alterations. 13 and 14 VBM studies for ADHD (619 patients and 483 controls) and SUDs (516 patients and 413 controls), respectively, were included. Patterns of decreased gray matter volume (GMV) were found in the left precentral gyrus, bilateral superior frontal gyri, and left inferior frontal gyrus in the ADHD group compared to the control group. In contrast, individuals with SUDs, relative to controls, were characterized by increased GMV in the left putamen and insula. Comparative analysis indicated larger regional GMV in the right inferior parietal lobule and smaller volumes in the left putamen and left precentral gyrus in the ADHD group than in the SUDs group. Dissociable brain structural abnormalities in adolescents and young adults with ADHD and SUDs potentially implicate different pathogeneses and provide a reference for differential diagnosis and early detection for shared symptomology and comorbidity.
... Substance use disorders, including cocaine use disorder (CUD), involve associative learning systems. Cocaine use can increase the salience of cocaine-paired cues that can drive continued use, craving, and relapse (Robinson and Berridge, 1993;Hyman, 2005). Cocaine-associated cues elicit strong physiological arousal and increased craving in individuals with CUD (Childress et al., 1988). ...
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Substance use disorder (SUD) is a chronic relapsing condition characterized by continued use of drugs despite negative consequences. SUD is thought to involve disordered learning and memory wherein drug-paired cues gain increased salience, and ultimately drive craving and relapse. These types of associations are thought to be encoded within sparsely distributed sets of neurons, called neuronal ensembles, that drive encoded behaviors through synchronous activity of the participant neurons. We have previously found that Fos-expressing neuronal ensembles within the prefrontal cortex are required for well-trained cocaine seeking. However, less is known about how quickly cortical neuronal ensembles form during the initiation of cocaine seeking behavior. Here, we seek to further elucidate the role of Fos-expressing neuronal ensembles within the prelimbic cortex (PL) after the initial acquisition of cocaine self-administration (SA), or, after 10 days of additional SA training (well-trained). We trained Fos-LacZ transgenic rats to lever press for cocaine under an FR1 schedule of reinforcement. Once rats met acquisition criteria for cocaine self-administration, we ablated Fos-expressing neuronal ensembles in the PL using the Daun02 inactivation method, either 1 or 10 days after the rats met the acquisition criteria. Targeted ablation of Fos-expressing neuronal ensembles in the PL attenuated active lever pressing both 1 day and 10 days after rats acquired cocaine self-administration. Together, this suggests that Fos-expressing neuronal ensembles rapidly form in the PL and continue to mediate maintained cocaine seeking behavior.
... Getting closer and closer to another individual sexually and/or romantically requires a trajectory that navigates from distal to proximal to interactive successfully. Attention and reward mechanisms are constantly at work during these phases, as they are in drug seeking (e.g., Robinson & Berridge, 1993). In fact, the well-known function of increased dopamine release in mesolimbic and preoptic terminal regions like the NAc and mPOA in response to sudden perturbations in reward expectancy (called "reward uncertainty"; Fiorillo, Tobler, & Schultz, 2003;Schultz, 2006) is likely to focus attention and arousal in situations in which the goal is an uncertain or moving target. ...
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In this chapter we review some of the multifarious roles of synchrony in mating psychology. We describe how synchronous dynamics contribute to the coherence of nervous systems; early bonding and development; and sexual and romantic relationships. While it is difficult to do justice to such a deep topic in a single chapter, we have attempted to provide a broad overview of ways in which rhythms have implications for understanding our social and emotional selves, and how our self-boundaries may expand to include others. Given the importance of wisely choosing and skillfully navigating this sort of co-mingling, we describe how varying degrees of intimacy can both gradually and precipitously build through patterns of synchronized rhythmic interactions, which both help to structure and gate the activities through which increasing degrees of closeness are shaped through mutually-rewarding experiences. While here we primarily focus on sexuality from a scientific and humanistic perspective, we believe these explorations point to how rhythmic interaction represents a keystone for our inherently intersubjective minds, allowing us to better understand some of the ways in which humans can be such a strange and extraordinary species.
... Exposure to drug cues during cocaine abstinence induces the activation of mesolimbic DA neurons, promoting an exaggerated incentive motivational state that primes individuals to seek drug and eventually relapse [60]. Consistent with this, prior evidence suggests that cocaine potency can influence behavior, with high cocaine potency associated with increases in cocaine self-administration and motivation to obtain cocaine [17,21,37], and reduced cocaine potency leading to reduced cocaine self-administration [21,61]. ...
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Relapse to drug use is one of the major challenges in treating substance use disorders. Exposure to drug-related cues and contexts triggers drug craving, which drives cocaine seeking, and increases the probability of relapse. Clinical and animal studies have shown a progressive intensification of cocaine seeking and craving that develops over the course of abstinence, a phenomenon commonly referred to as incubation of cocaine craving. Although the neurobiology underlying incubation of cocaine craving has been examined – particularly within the context of glutamate plasticity– the extent to which increased cocaine craving engenders mesolimbic dopamine (DA) changes has received relatively little attention. To assess whether incubation of cocaine craving is associated with alterations in DA terminal neurotransmission in the nucleus accumbens core (NAc), we used ex vivo fast scan cyclic voltammetry in female and male rats to assess DA dynamics following short access, long access, or intermittent access to cocaine self-administration followed by 28 days of abstinence. Results indicated that both long access and intermittent access to cocaine produced robust incubation of cocaine craving, which was associated with increases in cocaine potency. In addition, intermittent access self-administration also produced a robust increase in DA uptake rate at baseline. In contrast, short access to cocaine did not engender incubation of cocaine craving, nor produce changes in DA neurotransmission. Together these observations indicate that incubation of cocaine craving coincides with changes in DA transmission, suggesting that underlying changes in mesolimbic DA signaling may contribute to the progressive intensification of drug craving that occurs across periods of abstinence.
... This idea is supported by incentive-sensitisation theory (Robinson & Berridge, 1993). Robinson and Berridge argue that, through attribution, drug taking stimuli are more attention grabbing and that this attribution is mediated by changes in dopamine levels within the brain. ...
Thesis
p>The first section of this thesis presents a review on substance use and brain injury. The review identifies that a large percentage of individuals following brain injury are likely to use substances, both pre and post injury. This substance use can have an impact on rehabilitation and outcome. Therefore, this issue must be considered by clinicians working in the field of brain injury. There is limited evidence regarding treatment programmes, particularly in the UK. There has been no investigation into known predictors of relapse from the field of addictions such as cognitive flexibility and employment status. The study presented in the second part of the thesis aims to investigate the relationship between post-injury alcohol use and cognitive flexibility, post-injury productivity, pre-injury alcohol use and time since injury. A significant association was found between pre- and post-injury alcohol use, with trends towards significance with cognitive flexibility and post-injury productivity. However, these indices did not vary significantly for those identified as ‘at risk’ or ‘not at risk’. Regression analysis identified that pre-injury drinking and time since injury were significant predictors of post-injury drinking risk. The results indicate that brain injury services need to assess for alcohol use and to consider follow up procedures after discharge. More research is recommended investigating what other factors may contribute to this risk as time increases following the injury. In addition, it is recommended that time is spent examining the efficacy of treatment of alcohol use following brain injury, for example using modified CBT.</p
... Our models of such associations in meaning in this broader psychological sense could be analogous to semantic vectors, except for being acquired from learning experiences rather than a corpus of texts. The reinforcing effects of alcohol could then play a role in biasing the acquisition of alcohol-related meanings (Robinson and Berridge 1993;. ...
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Automatic associations involving alcohol have been proposed to play a role in drinking behavior. Such associations are often assessed using implicit measures such as the Implicit Association Test (IAT). Neural network language models provide computational measures of semantic relationships between words. These model-based measures could be related to behavioral alcohol-related associations as observed using the IAT. If so, this could provide a step toward better understanding of the nature of automatic associations and their relationship to behavior. The current study therefore aimed to test whether there is a systematic covariation over items between model-based and behavior-based associations. Analyses were performed for two single-target IATs from a previously published study. One task involved alcohol versus nonalcohol drinks and positive associates, and the other alcohol versus nonalcohol drinks and negative associates. The GenSim library and a pretrained word2vec model were used to calculate a relative computational association between specific items from the positive and negative categories, respectively, and the alcohol versus nonalcohol word sets. In both tasks, a significant covariance between items’ computational and behavioral measures of association was found over participants. The results thus add to the information on the relationship between neural network language models and psychological associations. They may provide methodological strategies for task design and data analysis. Models of semantic associations connect computational linguistics and social-cognitive psychology and may provide a theoretical link between measures of alcohol-related associations using verbal stimuli and alcohol-related cognition and behaviors.
... Alterations in monoaminergic neurotransmission have repeatedly been observed in subjects with major mental disorders. To highlight just a few findings, drug-induced dopamine release has been associated with attribution of incentive salience to drugassociated stimuli [40], while stress-dependent dopamine release may contribute to salience attribution to otherwise irrelevant stimuli in schizophrenia [41]. In humans, acute stress exposure was associated with an indirect measure of dopamine release in subjects with a history of low parental care only [42]. ...
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Social isolation and discrimination are growing public health concerns associated with poor physical and mental health. They are risk factors for increased morbidity and mortality and reduced quality of life. Despite their detrimental effects on health, there is a lack of knowledge regarding translation across the domains of experimental research, clinical studies, and real-life applications. Here, we review and synthesize evidence from basic research in animals and humans to clinical translation and interventions. Animal models indicate that social separation stress, particularly in early life, activates the hypothalamic-pituitary-adrenal axis and interacts with monoaminergic, glutamatergic, and GABAergic neurotransmitter systems, inducing long-lasting reductions in serotonin turnover and alterations in dopamine receptor sensitivity. These findings are of particular importance for human social isolation stress, as effects of social isolation stress on the same neurotransmitter systems have been implicated in addictive, psychotic, and affective disorders. Children may be particularly vulnerable due to lasting effects of social isolation and discrimination stress on the developing brain. The effects of social isolation and loneliness are pronounced in the context of social exclusion due to discrimination and racism, during widespread infectious disease related containment strategies such as quarantine, and in older persons due to sociodemographic changes. This highlights the importance of new strategies for social inclusion and outreach, including gender, culture, and socially sensitive telemedicine and digital interventions for mental health care.
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Purpose of Review Problematic pornography use (PPU) describes a pattern of behavior characterized by excessive time spent using or thinking about pornography and continued use despite negative consequences. To help advance the understanding of transdiagnostic underlying psychological and neurobiological mechanisms in PPU, we aim to review existing evidence on these mechanisms focusing on positive valence systems within the transdiagnostic Research Domain Criteria (RDoC) framework. Recent Findings Reward anticipation processes seem to be increased in individuals with PPU symptoms when they anticipate sexual stimuli compared with other rewards. Studies further suggest that the initial neural and attentional responses to sexual rewards compared with different control stimuli are also increased in individuals with PPU symptoms, as are conditioned responses in sexual reward learning paradigms. Sexual reward valuation studies point towards an increased neural value differentiation with increasing PPU symptoms. Summary The current state of evidence indicates that positive valence systems are altered in persons with PPU. This framework of organizing evidence may aid in elucidating PPU development and maintenance as well as planning future studies.
Thesis
p>The Incentive-Sensitisation Theory (IST) posits that reward is composed of distinct systems of ‘wanting’ and ‘liking’ that are mediated by separate neurobiological systems. The IST therefore claims that under certain conditions, wanting and liking can become dissociated. One of these conditions is repeated drug use. The IST claims that drug use results in a progressive and selective sensitisation of wanting but not liking. The current research sought to explore this dissociation between wanting and liking in humans using alcohol. Seven experiments tested the proposed dissociation using three methods of investigation. Method one (Experiments one and two) compared liking (facial electromyography (EMG), subjective ratings) for alcohol in groups of drinkers (heavy/light) that differed in wanting for alcohol. Method two (Experiments three to five) used a priming dose of alcohol to increase wanting (consumption, choice) independently of liking (facial EMG, subjective ratings) for alcohol. Method three (Experiments six and seven) decreased liking (ratings) independently of wanting (consumption) for alcohol by adulterating drinks with Tween. The results indicated a dissociation between wanting and liking for alcohol using all three methods. Liking could not explain the differences in wanting between light and heavy drinkers. Priming with alcohol resulted in increases in wanting but not liking for alcohol. Finally, adulterating an alcoholic beverage was found to decrease liking but not wanting for that alcoholic beverage. The results therefore provided support for the IST.</p
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Many people who generally receive standard recommended inoculations refuse to partake of COVID-19 vaccines, preventatives that are effective, safe, and life-saving amidst the current pandemic. Our quest is to understand this puzzling and dangerous phenomenon, as it exists among US and UK citizens, whom in other respects would be regarded as quite regular. We will discuss Vaccine Refusal compared with two better understood phenomena: addiction, and akrasia, along with the related matters of human action, intention, agency, will, and identity. Vaccine Refusal, we will argue, appears to be rewarded by "informational reinforcement" leading to heightened arousal, along with increases in self-esteem resulting from "bucking the trend," asserting one's "superior" understanding, and "tribal identity" in acting against social norms. These factors provide an overall reward amounting to satisfaction that outweighs the well-known consequences of COVID-19 infections. Our investigations will also lead us to a pair of epistemological hypotheses about two subtypes of the Vaccine Refusers under consideration here.
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Addiction is characterized by compulsive engagement despite adverse consequences. Psychobehavioral interventions targeting compulsivity in addictions are relatively rare, particularly for behavioral addictions like internet gaming disorder (IGD). Free from confounding drug-on-brain effects, IGD provides a promising model for understanding neuropsychological processes of addictions. IGD is a global concern in the setting of increasing internet use worldwide. Thus, developing interventions and understanding their mechanisms of action are important. Positive emotional association biases (EABs) towards addiction cues based on reward conditioning may underlie addiction-associated compulsivity. Here, we developed an EAB modification (EABM) protocol and examined whether modifying EABs via cognitive training would alter neurocognitive aspects of addiction-associated compulsivity in IGD. We recruited 90 IGD participants who were randomly assigned to receive EABM or sham training in a 1:1 ratio. The EABM intervention involved six consecutive days of exposure to negative emotional terms linked to gaming stimuli and positive terms linked to non-gaming healthy-alternative stimuli. The sham training involved similar stimuli linked to neutral words. Participants underwent event-related fMRI while performing a regulation-of-craving task and received several behavioral assessments pre-training and post-training. Primary efficacy measures were changes in gaming-related positive EABs, and compulsive gaming thoughts and behaviors. Behaviorally, EABM (vs. sham) training decreased gaming-related positive EABs and compulsive gaming thoughts and behaviors. Neurally, EABM training involved decreased activation in the bilateral dorsal striatum (DS) in the regulation-of-craving task, and altered left DS-centric functional connectivity with ventral prefrontal cortical regions, which correlated with decreases in gaming-related EABs or compulsive gaming thoughts and behaviors. EABM training also implicated activation changes in the right medial frontal gyrus and posterior insula. EABM may reduce compulsive gaming thoughts and behaviors via reshaping functional organization of fronto-striatal pathways and insular activity in IGD. The therapeutic potential of EABM should be examined in larger, longer-term studies, as should its application to other addictive disorders.
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Inappropriate food intake behavior is one of the main drivers for fat mass development leading to obesity. Importantly the gut microbiota-mediated signals have emerged as key actors regulating food intake acting mainly on the hypothalamus, and thereby controlling hunger or satiety/satiation feelings. However, food intake is also controlled by the hedonic and reward systems leading to food intake based on pleasure (i.e., non-homeostatic control of food intake). This review focus on both the homeostatic and the non-homeostatic controls of food intake and the implication of the gut microbiota on the control of these systems. The gut-brain axis is involved in the communications between the gut microbes and the brain to modulate host food intake behaviors through systemic and nervous pathways. Therefore, here we describe several mediators of the gut-brain axis including gastrointestinal hormones, neurotransmitters, bioactive lipids as well as bacterial metabolites and compounds. The modulation of gut-brain axis by gut microbes is deeply addressed in the context of host food intake with a specific focus on hedonic feeding. Finally, we also discuss possible gut microbiota-based therapeutic approaches that could lead to potential clinical applications to restore food reward alterations. Therapeutic applications to tackle these dysregulations is of utmost importance since most of the available solutions to treat obesity present low success rate.
Thesis
p>The first aim of the literature review is to explore current theories of addiction which consider the relationship between drug-related stimuli and drug use. The second aim of this review is to consider the relevant empirical research and, in particular, focus on the potential role of attentional bias and valence towards drug-related cues. The majority of the literature suggests that the drug-related cues are perceived as pleasant and attract attention (Mogg, Bradley, Field & De Houwer, 2003); however, some drug-related cues can also be perceived as unpleasant (Mutcha, Geier & Pauli, 1999). Therefore, there may be a dissociation between attentional bias and valence (Robinson & Berridge, 1993; 2001). The role of attentional bias and the perceived pleasantness of drug-related cues is one area which could further develop psychologists’ understanding of the mechanisms through which drug-related cues influence behaviour and inform clinical practice. The empirical paper investigates whether the perceived pleasantness of different types of smoking-related cues influence smokers’ attentional bias towards drug-related cues. Results of the study show that smoking-related cues hold attention (at 2000 ms, not 200 ms in a visual probe task) and elicit approach behaviours (stimulus response compatibility task), irrespective of their valence. These findings are consistent with Robinson and Berridge’s (1993; 2001) incentive-sensitisation theory of addiction, which suggests that there is a dissociation between ‘wanting’ and ‘liking’, in which attentional and approach biases for drug-related cues are independent of cue valence.</p
Thesis
p>The thesis commences with a literature review suggesting common neural circuits mediate food and drug rewards and discusses the application of behavioural and biological theories of addiction to overeating and obesity. Research exploring the relationship between food, reward and overeating is lacking. The current dominant neurobiological theory suggests reward can be separated into psychological components; ‘wanting’ (incentive salience attribution) and ‘liking’ (pleasurable/aversive evaluation) mediated by separate neural substrates. Features of overeating and addiction are discussed with the conclusion that there are many similarities. However, presence of tolerance and withdrawal effects, considered central to drug addiction, is weaker in overeating. Psychological processes of restraint, ambivalence and attribution appear to be more applicable to overeating. Although some authors maintain that labelling overeating as an addiction risks trivialising serious addictions, it is argued that the characterisation of overeating as an addiction is important as both issues are associated with serious health complications. The empirical study investigated if participants who were overweight showed an enhanced attentional or approach bias for food-related stimuli compared to participants of a healthy weight. The relationships between weight, attentional bias and implicit and explicit measures of stimulus valence were explored. Present findings suggest individuals who are overweight have reduced attentional bias for food cues compared with people of a healthy weight. Evidence of an over-responsive reward system (over-active dopamine system) in response to the sight of food was not present in participants who were overweight. Further research is needed to clarify the issue.</p
Article
Objectives Cognitive dysfunction and posttraumatic stress disorder (PTSD) are common in methamphetamine patients. However, few studies have investigated the cognitive performance of methamphetamine patients with PTSD. The purpose of this study was to investigate the impact of comorbid PTSD on cognitive function in Chinese male methamphetamine patients. Methods We analyzed 464 methamphetamine patients and 156 healthy volunteers. The PTSD Screening Scale (PCL-5) was used to assess PTSD and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was used to assess cognitive function. Results Compared with healthy controls, methamphetamine patients had more cognitive dysfunction in immediate memory, visuospatial/constructional, language, attention and delayed memory. Moreover, methamphetamine patients with PTSD had less cognitive dysfunction in immediate memory, attention, and delayed memory than methamphetamine patients without PTSD. Further stepwise regression analysis showed that PTSD alterations in arousal and reactivity cluster were risk predictors for language, and PTSD negative alteration in cognition and mood cluster were risk predictors for delayed memory. Conclusions Our results indicate that methamphetamine patients without PTSD have poorer cognitive dysfunction than those with PTSD. Some demographic and PTSD symptom clusters are protective or risk factors for cognitive dysfunction in methamphetamine patients.
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Incentive salience attribution can be understood as a psychobiological mechanism ascribing relevance to potentially rewarding objects and actions. Despite being an important component of the motivational process guiding our everyday behaviour its study in naturalistic contexts is not straightforward. Here we propose a methodology based on artificial neural networks (ANNs) for approximating latent states produced by this process in situations where large volumes of behavioural data are available but no experimental control is possible. Leveraging knowledge derived from theoretical and computational accounts of incentive salience attribution we designed an ANN for estimating duration and intensity of future interactions between individuals and a series of video games in a large-scale (N > 3 × 106) longitudinal dataset. We found video games to be the ideal context for developing such methodology due to their reliance on reward mechanics and their ability to provide ecologically robust behavioural measures at scale. When compared to competing approaches our methodology produces representations that are better suited for predicting the intensity future behaviour and approximating some functional properties of attributed incentive salience. We discuss our findings with reference to the adopted theoretical and computational frameworks and suggest how our methodology could be an initial step for estimating attributed incentive salience in large-scale behavioural studies.
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Substance use disorder is linked to impairments in the ventral tegmental area (VTA) dopamine (DA) reward system. Noradrenergic (NA) inputs from locus coeruleus (LC) into VTA have been shown to modulate VTA neuronal activity, and are implicated in psychostimulant effects. Phasic LC activity controls time- and context-sensitive processes: decision making, cognitive flexibility, motivation and attention. However, it is not yet known how such temporally-distinct LC activity contributes to cocaine seeking. In a previous study we demonstrated that pharmacological inhibition of NA signaling in VTA specifically attenuates cocaine-seeking. Here, we used virally-delivered opsins to target LC neurons for inhibition or excitation, delivered onto afferents in VTA of male rats seeking cocaine under extinction conditions. Optogenetic stimulation or inhibition was delivered in distinct conditions: upon active lever press, contingently with discreet cues; or non-contingently, i.e., throughout the cocaine seeking session. Non-contingent inhibition of LC noradrenergic terminals in VTA attenuated cocaine seeking under extinction conditions. In contrast, contingent inhibition increased, while contingent stimulation reduced cocaine seeking. These findings were specific for cocaine, but not natural reward (food) seeking. Our results show that NA release in VTA drives behavior depending on timing and contingency between stimuli – context, discreet conditioned cues and reinforcer availability. We show that, depending on those factors, noradrenergic signaling in VTA has opposing roles, either driving CS-induced drug seeking, or contributing to behavioral flexibility and thus extinction.
Article
Neuroimaging studies have identified a variety of brain regions whose activity predicts substance use (i.e., relapse) in patients with substance use disorder (SUD), suggesting that malfunctioning brain networks may exacerbate relapse. However, this knowledge has not yet led to a marked improvement in treatment outcomes. Noninvasive brain stimulation (NIBS) has shown some potential for treating SUDs, and a new generation of NIBS technologies offers the possibility of selectively altering activity in both superficial and deep brain structures implicated in SUDs. The goal of the current review was to identify brain structures involved in relapse to SUD and give an account of innovative methods of NIBS that might be used to target deeper brain structures than have been possible previously. Included studies measured fMRI in currently abstinent SUD patients and tracked treatment outcomes, and fMRI results were organized with the framework of the Addictions Neuroclinical Assessment (ANA). Four brain structures were consistently implicated: the anterior and posterior cingulate cortices, ventral striatum and insula. These four brain structures may be appropriate future targets for the treatment of SUD using these innovative NIBS technologies.
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Consumption and its excesses are sometimes explained by imbalance of need or lack of control over “wanting.” “Wanting” assigns value to cues that predict rewards, whereas “needing” assigns value to biologically significant stimuli that one is deprived of. Here we aimed at studying how the brain activation patterns related to value of “wanted” stimuli differs from that of “needed” stimuli using activation likelihood estimation neuroimaging meta‐analysis approaches. We used the perception of a cue predicting a reward for “wanting” related value and the perception of food stimuli in a hungry state as a model for “needing” related value. We carried out separate, contrasts, and conjunction meta‐analyses to identify differences and similarities between “wanting” and “needing” values. Our overall results for “wanting” related value show consistent activation of the ventral tegmental area, striatum, and pallidum, regions that both activate behavior and direct choice, while for “needing” related value, we found an overall consistent activation of the middle insula and to some extent the caudal‐ventral putamen, regions that only direct choice. Our study suggests that wanting has more control on consumption and behavioral activation.
Article
Background Reward sensitivity is a dimensional construct central to understanding the nature of depression. Psychophysiological research on this construct has primarily focused on the reward positivity (RewP), an event-related potential (ERP) that indexes consummatory reward sensitivity. The current study extended prior research by focusing on ERPs that index the motivational component of reward. Methods A novel effort-for-reward task was used to elicit motivational and consummatory ERPs. Groups consisting of 34 depressed and 32 non-depressed participants were compared across a range of reward-related ERPs. Results Depressed participants exhibited reduced P3 response to effort completion cues following high effort expenditure, reduced anticipation of rewards after low effort expenditure (i.e., the stimulus preceding negativity), and reduced RewP following high effort expenditure. ERPs occurring prior to reward receipt accounted for unique variance in depression status and differentiated between subgroups of depressed individuals. Conclusions Findings support the utility of leveraging multiple ERPs that index separate reward processing deficits to better characterize depression and depressive subtypes.
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Rationale Addiction is characterized by intermittent drug seeking despite rising costs. This behavior is heavily influenced by environmental stimuli that signal drug availability and reinforce drug seeking. Objective To establish the relationship between three key aspects of human drug use in rats: the intermittent, binge nature of drug intake, the motivational conflict of drug seeking in the face of escalating negative costs, and the ability of different drug cues to interact to modulate relapse. Methods Male and female rats were trained to self-administer cocaine on an intermittent access schedule, where brief drug-availability states were signaled by a shift in the ambient lighting of the environment, and cocaine infusions were signaled by a separate proximal discrete cue. Rats then went through a conflict procedure, where foot shock intensity associated with cocaine seeking was escalated until intake was suppressed. We then completed relapse tests where the drug-delivery cue was noncontingently presented alone, or in the context of dynamic drug-availability state transitions. Results Intermittent access spurred psychomotor sensitization and binge-like cocaine intake. The intensity of binge-like drug taking during training was predictive of later drug seeking despite escalating costs during conflict. In relapse tests, the ability of a proximal discrete drug cue to trigger relapse was gated by the presence of a global cue signaling drug-availability state transitions. Conclusions Our results suggest that the pattern of drug intake plays a role in many features of addiction, including modifying an individual’s willingness to endure high costs associated with drug seeking. Furthermore, our studies indicate that drug-related sensory information can be hierarchically organized to exert a dynamic modulating influence on drug-seeking motivation.
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Several experimental paradigms were developed to measure attentional biases towards alcohol-related cues. However, most of them are based on reaction times to two-dimensional stimuli displayed on a computer screen, such that their ecological validity has been questioned. To address this, we integrated an eye tracking system into a virtual reality headset (ET-VR) and measured attentional biases in a subclinical population of alcohol users. In this exploratory study, forty social drinkers were recruited and immersed in a virtual bar including alcohol-related stimuli. Attentional focus was assessed using dwell time and number of fixations for these alcohol-related stimuli as well as for neutral stimuli unrelated to alcohol consumption. The results show that the number of fixations and, to a lesser extent, the dwell time for alcohol-related cues were positively correlated with the drinking motivation of the participants. In contrast, no significant correlation was found for neutral stimuli. In conclusion, the present study shows that alcohol-induced attentional biases can be studied using an ET-VR device in a subclinical population of alcohol users.
Article
Cue-based associative learning (i.e., Pavlovian conditioning) is a foundational component of behavior in almost all forms of animal life and may provide insight into individual differences in addiction liability. Cues can take on incentive-motivational properties (i.e., incentive salience) through Pavlovian learning. Extensive testing with non-human animals (primarily rats) has demonstrated significant variation among individuals in the behaviors this type of learning evokes. So-named “sign-trackers” and “goal-trackers” have been examined in many studies of non-human animals, but this work in humans is still a nascent area of research. In the present proof-of-concept study, we used a Pavlovian conditioned approach task to investigate human sign- and goal-tracking in emerging adults. Conditioned behaviors that developed over the course of the task were directed toward the reward-cue and toward the reward location. Participants’ eye-gaze and behavior during the task were submitted to a latent profile analysis, which revealed three groups defined as sign-trackers (n = 10), goal-trackers (n = 4), and intermediate responders (n = 36). Impulsivity was a significant predictor of the sign-tracking group relative to the goal-tracking group. The present study provides preliminary evidence that a simple procedure can produce learned Pavlovian conditioned approach behavior in humans. Though further investigation is required, findings provide a promising step toward the long-term goal of translating important insights gleaned from basic research into treatment strategies that can be applied to clinical populations.
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An integrative model of sexual addiction is presented, involving a combination of models based upon (i) incentive motivation theory and (ii) the dual organisation of the control of behavior. The model is related to ongoing arguments about the validity of the notion of addiction when applied to sexual behavior. It is suggested that the evidence strongly favors the viability of an addiction model of sex. Strong similarities to the classical addiction to hard drugs are observed and features can be better understood with the help of the model. These include tolerance, escalation and withdrawal symptoms. It is argued that other candidates for accounting for the phenomena, such as obsessive-compulsive behavior, faulty impulse control, high drive and hypersexuality do not fit the evidence. The role of dopamine is central to the model. The model’s relevance to stress, abuse, development, psychopathy, fantasy, sex differences, evolutionary psychology and the interaction with drug-taking is shown.
Chapter
Emerging clinical and pre-clinical evidence is providing a convergent understanding of the impacts of adolescent cannabinoid exposure on the developing brain. The correlational limitations of clinical studies are being supplemented with important new mechanistic studies using rodent models of adolescent cannabinoid exposure to reveal the precise underlying neuronal, molecular and behavioral mechanisms related to how neurodevelopmental exposure to cannabinoids such as delta-9-tetrahydrocannabinol (THC) may cause increased risk for serious neuropsychiatric disorders like addiction, anxiety disorders and schizophrenia. In particular, the ability of adolescent cannabinoid exposure to profoundly alter dopamine, GABA and glutamate signaling pathways and their associated molecular effectors, has revealed specific biomarkers related to how adolescent cannabinoid exposure increases long-term risks for neuropsychiatric disorders. This chapter will highlight several lines of pre-clinical evidence revealing how cannabinoid transmission in the mammalian brain can regulate emotional processing and cognition in specific mesocorticolimbic circuits. These findings will be discussed in the context of human clinical findings related to the effects of cannabinoids on neuropsychiatric risk and consider how these pathophysiological sequelae may set the stage for increased vulnerability to these disorders later in life.
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Repeated amphetamine treatment results in locomotor sensitization, a phenomenon that may relate to the development of psychosis and addiction. Evidence suggests that interactions between dopaminergic and glutamatergic systems are involved in amphetamine sensitization. We previously demonstrated that the neuronal excitatory amino acid transporter (Slc1a1/EAAT3) produces bidirectional, expression-dependent effects on the response to acute amphetamine. Here, using mice with decreased or increased expression of EAAT3, we found that chronic alterations in EAAT3 expression do not significantly impact amphetamine-induced locomotor sensitization. Compensation by other glutamate transporters cannot be ruled out in this important neuroadaptive phenomenon.
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Attentional bias plays a vital role in the occurrence and development of addictive behaviors. However, little is known about attentional processes in problematic Internet pornography use (PIPU), and previous studies have reported mixed results. The current study examined the components of attentional processing to sexual stimuli using an exogenous cueing task designed to differentiate between attentional engagement and disengagement. Two different stimulus presentation times (100 and 500 ms) were used to present the pornographic and neutral images to differentiate the early and late stages of attentional bias. Individuals with high (n = 40) and low (n = 40) PIPU tendencies were compared. The results demonstrated that individuals with high tendencies toward PIPU showed enhanced attentional engagement with pornographic stimuli in the early stage of attentional processing (100 ms), followed by attentional avoidance in the late stages of attentional processing (500 ms). Moreover, the severity of PIPU symptoms was positively correlated with attentional engagement scores in the short picture-time trials (100 ms) and weakly negatively correlated with attentional disengagement scores in the long picture-time trials (500 ms). This approach–avoidance pattern of attentional biases is in line with a recent theoretical model that emphasizes that appetitive and aversive motivational processes jointly determine attentional bias.
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Obesity represents a risk factor for disability with a major bearing on life expectancy. Neuroimaging techniques are contributing to clarify its neurobiological underpinnings. Here, we explored whether structural brain abnormalities might accompany altered brain activations in obesity. We combined and compared data from brain activation studies for food stimuli and the data reported in structural voxel-based morphometry studies. We found that obese individuals have reduced grey matter density and functional activations in the thalamus and midbrain. A functional connectivity analysis based on these two clusters and its quantitative decoding showed that these regions are part of the reward system functional brain network. Moreover, we found specific grey matter hypo-densities in prefrontal cortex for the obese subjects, regions involved in controlled behaviour. These results support theories of obesity that point to reduced bottom-up reward processes (i.e., the Reward Deficit Theory), but also top-down theories postulating a deficit in cognitive control (i.e., the Inhibitory Control Deficit Theory). The same results also warrant a more systematic exploration of obesity whereby the reward of food and the intentional control over consummatory behaviour is manipulated.
Article
Given the vulnerability of older adults to chronic disease and physical disability, coupled with the threat that obesity poses to healthy aging, there is an urgent need to understand the causes of positive energy balance and the struggle that many older adults face with intentional weight loss. This paper focuses on neural vulnerabilities related to overeating in older adults, and moderating variables that can have either favorable or unfavorable effects on these vulnerabilities. Research from our laboratory on older adults with obesity suggests that they are prone to similar neural vulnerabilities for overeating that have been observed in younger and middle‐aged populations. In addition, following brief postabsorptive states, functional brain networks both in the resting state and in response to active imagery of desired food are associated with 6‐month weight loss. Data reviewed suggest that the sensorimotor network is a central hub in the process of valuation and underscores the central role played by habits in overeating. Finally, we demonstrate how research on the neural vulnerabilities for overeating offers a useful framework for guiding clinical decision‐making in weight management. A neural‐based model of key concepts and moderating variables influencing eating behavior.
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The Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5) definition of alcohol use disorder (AUD) has been criticized on the ground that it leads to high prevalence rates and a highly heterogeneous group. Failure of the DSM to consider development may exacerbate these issues (e.g., conflating experimentation with problematic drinking). Wakefield and Schmitz (2015) proposed a definition of AUD that comports to the harmful dysfunction (HD) theory of mental disorders while data-driven approaches have suggested that key symptoms like craving, failure to fulfill obligations, hazardous use, and alcohol use despite interpersonal consequences are optimal (OPT) criteria for AUD (Stevens et al., 2019). Prior work suggests both may reduce the likelihood of conflating experimentation with problematic drinking during key developmental periods. Continuous and categorical structural equation models of DSM, HD, and OPT criteria were compared on A) prevalence, B) patterns of alcohol use in adolescence (age 10–18 years) C) early AUD symptoms in adolescence (age 13–15) and D) concurrent alcohol use and alcohol consequences to assess prospective and concurrent convergent validity using a longitudinal design (N = 765; ages 10–21 years). Results supported prior literature that the HD and OPT criteria produced a smaller diagnostic class than the DSM. Furthermore, the HD and OPT criteria had larger and more consistent effects with validators than the DSM with the OPT criteria having the largest effects and the least criteria. Future work should consider whether the OPT or HD criteria better reflect AUD severity than the DSM across development.
Chapter
Drug abuse or substance abuse disorder is a widespread problem, and is considered both a brain disorder and a form of mental illness. Many types of drugs can be abused, including opiates and the stimulants cocaine and methamphetamine. Although initial drug use is voluntary, once established addiction involves changes in the brain and is no longer entirely amenable to self-control. Drug use does not inevitably lead to addiction. Certain stimulants, such as caffeine, have little or no harmful effect. Many drugs can stimulate dopamine systems, either directly as in the case of cocaine and amphetamines or indirectly. Cannabinoid and opiate systems are also involved in addiction. Drugs can directly stimulate motivational systems through activation of dopamine neurotransmission, but chronic drug use causes changes in the brain and adaptations in regulatory proteins such as CREB. These adaptations can alter dopamine system function resulting in dysfunction of reward mechanisms. Gambling, and possibly eating, thrill seeking, stealing, shopping, sexual behavior, internet use, exercise, smartphone use, and online gaming can have addiction-like properties, although currently only gambling is recognized as an addictive disorder.KeywordsDrugSubstance abuseSubstance abuse disorderSubstance use disorderAddictionStimulantMarijuanaTetrahydrocannabinolTHCOpiumMorphineOpioidCocaineCocaBrain disorderMental illnessAmphetamineCocaineKetamineKhatBetel nutHallucinogensNitrous oxideTolueneInhalantsSynthetic opiatesMDMAEcstasyCaffeineTheobromineTheophyllineMethamphetamineFentanylCREBΔFosBIRS2-AktAP-1 - AKT-m - TORC2 - MEF2GamblingStealingShoppingSexual behaviorInternet useExerciseSmartphone addictionOnline gamingEatingThrill seeking
Article
Aims : Consistent with the opponent process theory individuals with chronic opioid use should predominantly endorse the avoidance of aversive negative emotional and/or physiological states as the motivation for continued opioid use (source of reinforcement: reductions in negative states). The primary aim of this study was to explore whether this view is supported by the subjective effects of heroin reported by individuals with opioid use disorder (OUD). Methods : Responses during in-person interviews of participants to the question “What do you like about heroin?” were categorized as positive, negative, or mixed (positive and negative) reinforcement. In addition, we examined differences between these “reinforcement groups” in sociodemographic and clinical variables. Results : Participants (N=307) with OUD were predominantly male (78.1%), with chronic heroin use (M=15.8 years, SD=11.5), and 46.1% currently used heroin and were not enrolled in treatment. Agreement between two raters concerning the categorization of participant-reported effects of heroin into reinforcement categories was high, κ=.924, p<.0005. Approximately half (49.8%) of participant-reported effects of heroin were categorized as attributable to positive reinforcement. About one-fourth (22.8%) were categorized as negative reinforcement and 9.0% as “mixed”. There were no statistically significant differences between the three reinforcement groups in any of the socio-demographic variables, duration of heroin use, or treatment status/interest. Conclusions : The results of this study indicate marked heterogeneity of heroin effects experienced by individuals with OUD and their source of reinforcement, respectively. Better integration of how individuals construe their drug use is important to understand the psychological—and neurobiological—processes in the development and maintenance of OUD.
Article
Background: Attentional bias (AB) has been linked to alcohol use, mood, and alcohol craving, with key differences across different types of mood and biological sex. However, further exploration of the role of AB across these alcohol variables is needed. The current study examined the relationship between mood and AB as predictors of alcohol craving using ecological momentary assessment (EMA). Exploratory analysis examined these effects as a function of biological sex. Methods: Participants (n = 69) from a Midwestern University carried a mobile device for 15 days and provided ratings of momentary mood (positive mood, anxious mood, and sad mood), alcohol craving, and AB. Data were analyzed using a two-level multilevel regression model, with associations between craving, mood, and AB examined at both the momentary and between-subjects levels. Results: Across assessments, positive and negative moods were positively associated with momentary craving, with AB found to operate differently between men and women. At the within-subjects level, increases in positive mood among men strengthened the AB-craving association, while women showed stronger AB-craving associations when positive mood decreased. At the between-subjects level, trait-like sadness led to positive AB-craving associations for men, however, this was the opposite for women. Similarly, AB-craving associations were positive and robust for men with trait-like positive mood but again the opposite was observed for women. Conclusions: The findings highlight the importance and nuances of biological sex in the context of mood, AB, and craving. Interventions targeting AB and/or emotion regulation may yield different outcomes for men and women.
Article
Background Although previous studies have investigated the role of attentional bias in gambling, the inconsistent findings and the paucity of research require further investigations, as well as the examination of the interrelationships between attentional bias, subjective craving, and gambling severity. Methods The present study comprised 80 male gamblers, aged between 18 and 64 years. Participants carried out a modified version of the Posner Task to assess attentional bias and completed the South Oaks Gambling Screen (SOGS) and the Gambling Craving Scale (GACS) to assess the severity of gambling involvement and the subjective gambling-related craving, respectively. Results Regression analyses showed that craving and facilitation bias at 500 ms are significant predictors of gambling severity. The path analysis indicated that craving predicted gambling severity not only directly, but also indirectly via attentional bias for gambling stimuli. Limitations The recruitment of male participants and the not-matched gambling stimuli to the preferred gambling activity limit the present results. Conclusions The present findings shed light on the interrelationships between craving, attentional bias, and problem gambling, demonstrating that craving is indirectly associated with problem gambling via attentional bias: higher levels of craving make gamblers more responsive to gambling cues, leading to attentional bias, which, in turn, motivate gamblers to bet, contributing to problematic gambling.
Article
Background The comorbidity between substance use disorder and major depressive disorder is a typical dual diagnosis in the field of substance addiction. However, the prevalence and correlates of depression in methamphetamine addicts and whether it is associated with drug craving and alexithymia have been rarely reported in the Chinese population. Methods We recruited 585 methamphetamine-dependent males from a drug rehabilitation center in China and 203 healthy controls. Demographic and drug use data were collected. Depression was assessed using the Mini International Neuropsychiatric Interview (M.I.N·I.). Methamphetamine cravings and alexithymia were assessed using the Desire for Drugs Questionnaire (DDQ) and the Toronto Alexithymia Scale (TAS). Results The prevalence rate of depression in methamphetamine-dependent men was 16.58 % (97/585). The scores of DDQ desire and intention, DDQ negative reinforcement, total DDQ, difficulty identifying feelings (DIF), difficulty describing feelings (DDF), and total TAS score of depressed patients were higher than those of non-depressed patients. However, only DDQ negative reinforcement score, DIF, DDF, and total TAS score remained significant after Bonferroni correction. Additionally, logistic regression analysis found that age, DIF score, and DDQ negative reinforcement score were significant factors contributing to depression in methamphetamine-dependent men. Conclusion Our findings suggest that the prevalence of depression is significantly higher in methamphetamine-dependent men than in the healthy Chinese population. Furthermore, age, components of alexithymia and drug craving are risk factors for depression in methamphetamine addicts.
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Food attention bias could be used to indicate diet-related diseases in individuals with obesity. The purpose of this study is to explore the relationship between body mass index (BMI) and food attention bias, and the mediating role of body weight dissatisfaction (BWD) on this relationship in women. Seventy-five participants were recruited to complete a visual dot task with eye tracking. The results showed that BMI would positively predict response latency and duration bias on high-calorie foods; the relationship between BMI and response latency of high-calorie food was a complete mediation of BWD; the relationship between BMI and duration bias of high-calorie food was a complete mediation of BWD; and BWD positively predicts response latency and duration bias on high-calorie foods. These findings suggest a positive relationship between BMI and food attention bias, and the effect of a complete mediation of BWD in women.
Thesis
p>Stimuli in the environment can become associated with drug use and act as cues to maintain drug-taking. A number of psychological theories have proposed mechanisms through which cues may influence behaviour. These are discussed in the literature review and the conclusion is drawn that research is needed that tests the specific predictions made by the currently influential models. The investigation of cognitive biases that influence response to cues is highlighted as one area that could be investigated by psychologists in the field. An attentional bias towards drug-related stimuli has been shown in dependent subjects across substances. The empirical paper investigates the nature of this bias. The results showed a significant attentional bias for drug related information in opiate dependent subjects when the stimuli were presented for 200ms in a dot probe task. There was no evidence of an attentional bias when the stimuli were presented for 500 or 1500ms. It is suggested that 200ms reflects an automatic level of information processing which will guide behaviour without the engagement of strategic cognitive processes. This supports the incentive-sensitisation mechanism suggested by Robinson & Berridge (1993). The clinical implications of this are discussed in terms of cognitive behavioural interventions.</p
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Reactions of novices to opiate range from extremely positive to completely negative, and the role of these effects play in forming a drug habit has interested both scholars concerned with explaining the spread of heroin addiction and physicians troubled over the hazards of administering opiate medications. Although some observers have recently questioned heroin's euphoriant potential, research shows that many "normals" in laboratory studies and a majority of addicts on the street felt some euphoria during their first trial with an opiate. The higher proportion of euphoric responses among future addicts, commonly explained by reference to the prevalence of psychopathology in addict populations, is probably due to other differences as well. Subsequent opiate use where effects were unpleasant can still be traced to a continued interest in euphoria. Negative reactions caused some neophytes to discontinue use, but addicts-to-be were more motivated and learned from experienced users that undesirable side effects could be discounted as temporary and virtually all the addicts-to-be did achieve euphoria in a few tries. Thus, pre-dependence heroin use is explained by pleasurable drug effects, but when exposure to euphoria occurs in a medical context, the risk of addiction is minimal.
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Noncontingent “priming” presentations of positive reinforcers (or incentive events) can enhance and reinstate previously acquired instrumental responding for these reinforcers. We describe how this phenomenon may be used to study the motivational control of drug-taking behavior and the relapse to drug-taking in drug-free individuals.
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Taste substances applied to the oral cavity result in either ingestion or rejection, each with a characteristic muscular response pattern. These responses are the same in decerebrate and intact rats; the caudal brainstem appears to be the neural substrate of ingestion and rejection responses. The experiment determined whether decerebrates can alter these discriminative responses as a function of food deprivation or toxicosis. Food-deprived decerebrate rats, like intact ones, ingested a taste substance they had rejected when sated. However, these same decerebrates, in contrast to controls, neither rejected nor decreased ingestive reactions to a novel taste after that taste had been repeatedly paired with lithium chloride-induced illness. Although the forebrain may be important for integrating ingestion, some aspects of this control seem to be represented in caudal brain areas.
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Evidence is reviewed which suggests that there may be little or no direct introspective access to higher order cognitive processes. Subjects are sometimes (a) unaware of the existence of a stimulus that importantly influenced a response, (b) unaware of the existence of the response, and (c) unaware that the stimulus has affected the response. It is proposed that when people attempt to report on their cognitive processes, that is, on the processes mediating the effects of a stimulus on a response, they do not do so on the basis of any true introspection. Instead, their reports are based on a priori, implicit causal theories, or judgments about the extent to which a particular stimulus is a plausible cause of a given response. This suggests that though people may not be able to observe directly their cognitive processes, they will sometimes be able to report accurately about them. Accurate reports will occur when influential stimuli are salient and are plausible causes of the responses they produce, and will not occur when stimuli are not salient or are not plausible causes.
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Studies of human amnesia and studies of an animal model of human amnesia in the monkey have identified the anatomical components of the brain system for memory in the medial temporal lobe and have illuminated its function. This neural system consists of the hippocampus and adjacent, anatomically related cortex, including entorhinal, perirhinal, and parahippocampal cortices. These structures, presumably by virtue of their widespread and reciprocal connections with neocortex, are essential for establishing long-term memory for facts and events (declarative memory). The medial temporal lobe memory system is needed to bind together the distributed storage sites in neocortex that represent a whole memory. However, the role of this system is only temporary. As time passes after learning, memory stored in neocortex gradually becomes independent of medial temporal lobe structures.
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Evidence from several research areas suggests that response-dependent and independent presentation of environmental events have different neurobiological consequences. Investigations of neurotransmitter turnover rates and cholinergic muscarinic receptor densities in brain regions of rats receiving contingent and noncontingent intravenous morphineresulted in the identification of two neuronal networks that are involved in response dependent morphine presentation. These circuits are concordant with brain regions showing increased glucose utilization in animals receiving response-dependent electrical stimulation of either the substantia nigra or ventral tegmental area. These data indicate substantial differences between contingent and noncontingent presentation of environmental events and suggest that neurobiological investigations of reinforcement that use response independent delivery of a putative reinforcer must be interpreted with some caution.
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Progress has been made over the last 10 years in determining the neural mechanisms of sensitization induced by amphetamine-like psychostimulants, opioids and stressors. Changes in dopamine transmission in axon terminal fields such as the nucleus accumbens appear to underlie the expression of sensitization, but the actions of drugs and stressors in the somatodendritic regions of the A10/A9 dopamine neurons seem critical for the initiation of sensitization. Manipulations that increase somatodendritic dopamine release and permit the stimulation of D1 dopamine receptors in this region induce changes in the dopamine system that lead to the development of long-term sensitization. However, it is not known exactly how the changes in the A10/A9 region are encoded to permit augmented dopamine transmission in the terminal field. One possibility is that the dopamine neurons of sensitized animals have become increasingly sensitive to excitatory pharmacological and environmental stimuli or desensitized to inhibitory regulation. Alternatively, changes in cellular activity or protein synthesis may result in a change in the presynaptic regulation of axon terminal dopamine release.
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Dopamine neurons in behaving animals respond in a stereo-typed and homogeneous fashion to salient external stimuli that attract the attention of the subject. Depending on the particular behavioural situation, dopamine neurons are activated by novel, unexpected stimuli, by primary rewards in the absence of predictive stimuli and during learning, and by conditioned incentive stimuli predicting reward and eliciting a behavioural reaction. Thus dopamine neurons signal the presence of an important stimulus that needs to be processed by the subject with high priority, without specifying details of the stimulus other than its motivational significance or salience. These data provide neurophysiological correlates for the involvement of dopamine neurons in central processes determining the behavioural reactivity of the subject to important environmental events.
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environmental specificity of tolerance / morphine tolerance / non-opiate drugs Pavlovian conditioning situation / drugs as UCSs [unconditioned stimuli] / drug compensatory CRs [conditioned responses] / compensatory CRs and tolerance relationship between conditioning and non-associative interpretations of tolerance evidence for conditional model of tolerance / cues for drugs Pavlovian conditioning and drug dependence / role of self-administration (PsycINFO Database Record (c) 2012 APA, all rights reserved)
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describe one of our early studies of defensive burying to illustrate our methodological approach to the study of rat defensive behavior / describe how we have recently adapted this approach to the study of maternal defensive behavior / describe two recent studies that challenge the assumption that rats typically avoid well-defined inanimate sources of noxious stimulation (PsycINFO Database Record (c) 2012 APA, all rights reserved)
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designed to meld three traditions: the study of the nervous system, the study of behavior, and the study of mental processes self-injection unicellular animals / flies / sea slug, "Aplysia" / garden slug, "Limax Maximus" / brain-transected rats / brain lesioned rat / neurochemically impaired rat single neurons in a normal brain angiotensin and fluid pressure vasopressin and osmotic balance aldosterone, naturetic factor and sodium balance cholecystokinin and digestion neurotensin and lipostasis TRH [thyrotropin-releasing hormone] and calorigenesis insulin and the absorptive state ACTH [adrenocorticotropin] and stress opiods in stress and feeding LHRH [leutinizing hormone releasing hormone] and reproductive functions intracerebral self-injection (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Article
The sway that the response-reinforcement framework (Spencer, Thorndike, Hull, Skinner) has held on the behavioral sciences for nearly a hundred years is finally ending. The strength of this framework lay in providing concepts and methods for studying the effects of hedonic (reinforcing) stimuli on the repetition of specified responses acquired in instrumental training situations of various kinds. Its weakness lay in the invalidity of its central assumptions, stimulus-response association and response-reinforcement, which could not deal with motor-equivalence and flexibility (or “intelligence”) in behavior. To the four decades of incisive criticism on particular theoretical and empirical grounds, a more comprehensive challenge to the response-reinforcement framework is now added by the newer ideas about the nature of cognitive, motivational, and response-production processes that have emerged from the work of ethologists, neuroscientists, and cognitive psychologists. An alternative framework, incorporating the newer ideas, is clearly needed. The particular framework proposed here is based on the ideas of perceptual learning of stimulus-stimulus correlations and of a motivational (rather than reinforcing) role of hedonic (incentive) stimuli. According to it, an act is produced when its act-assembly is activated by a pexgo (perceptual representation) of a certain eliciting stimulus complex (ES). When certain eliciting stimuli are correlated with incentive stimuli, they acquire motivational properties that serve to strengthen the pexgos generated by those eliciting stimuli and thereby increase the probability of activation of the corresponding act-assemblies. Motivation thus influences response production, not by directly instigating “existing” responses, but by modulating the strength of pexgos of eliciting stimuli for the succession of acts that comprise a response. Therefore, a response is always constructed afresh on the basis of current perceptions; not even a stable and stereotyped response occurs as a mere activation of a preformed motor program. The topography of any response that emerges is determined by the nature of the motivational state and the momentary spatiotemporal distribution of eliciting stimuli of changing motivational valence. By suggesting that the animal learns the overlapping and nested correlations between the stimulus events that commonly occur in a given situation, and by separating what is learned from the processes of response production, the proposed perceptual-motivational framework seems capable of dealing with the problems of motor equivalence and flexibility in adaptive behavior. Some implications of this approach for further behavioral and brain research on such problems as behavior modification, learning by observation of models, analysis of causality, and search for neural substrates of learning and response production, are outlined.
Article
It is well known that benzodiazepines produce dependence in humans and locomotor stimulation in experimental animals. In this study the possible involvement of catecholamines in the diazepam-induced locomotor stimulation in mice were investigated. Diazepam was found to have a biphasic effect; increasing locomotor activity at a low dose (0.25 mg/kg), while decreasing it at higher doses (>0.5 mg/kg). The locomotor stimulating effect of diazepam was effectively blocked by pretreatment with the benzodiazepine receptor antagonist flumazenil, as well as with the catecholamine synthesis inhibitor -methyltyrosine and the dopamine receptor antagonists haloperidol, spiperone and SCH 23390. Taken together, these data indicate that the locomotor stimulating effect observed after low doses of diazepam is due to activation of brain dopaminergic systems involved in locomotor activity. The observations are discussed in relation to the hypothesis that dependence-producing drugs activate specific brain reward systems.
Article
The acquisition of low-dose (0.25 mg/kg/infusion) intravenous cocaine self-administration was measured in rats that had received nine daily injections of amphetamine (1.0 mg/kg, IP), nicotine (0.6 mg/kg base weight, SC) or vehicle. For control rats, the acquisition of self-administration was gradual with the number of responses per 2 h daily test session increasing between days 3 and 9. By comparison, rats preexposed with amphetamine and nicotine demonstrated elevated response means during the early days of testing, suggesting more rapid acquisition. All groups eventually reached similar asymptotic levels of responding. The enhanced responding observed during the early days of testing in the rats preexposed with amphetamine and nicotine was due to an increased number of subjects that reliably self-administered cocaine. Thus, the rats preexposed with amphetamine and nicotine seemed predisposed to the reinforcing effects of cocaine. In contrast to the self-administration data, preexposure to nicotine failed to sensitize rats to the locomotor activating effects of cocaine. In fact, the same preexposure regimen appeared to produce tolerance to this effect of cocaine. These data give evidence that different mechanisms may mediate sensitization to the reinforcing and locomotor activating effects of cocaine.
Article
In rats treated with phenyclidine (PCP) repeatedly (PCP 10 mg/kg per day for 14 days), the back-pedalling, head-weaving and turning induced by PCP were attenuated (tolerance), while PCP-induced sniffing, rearing and ambulation were potentiated (supersensitivity). The behavior induced by the direct and indirect serotonin (5-HT) agonists, 5-methoxy-N,N-dimethyltryptamine and p-chloroamphetamine, was attenuated, while the sniffing, rearing or licking induced by the direct and indirect dopamine (DA) agonists, apomorphine and methamphetamine, were potentiated in the chronic PCP-treated rats. The DA and 5-HT contents in the nucleus accumbens and the ratio of HVA to DA in the striatum increased following the repeated PCP administration. Pentobarbital-induced sleep time did not change in the chronic PCP-treated rats as compared with the control rats. In addition, there was no significant difference between the disappearance rate of PCP in the brain of the rats treated with PCP repeatedly and the rate in the control rats. These results suggest that functional changes in the dopaminergic and serotonergic neuronal systems develop on repeated administration of PCP but that such changes do not develop in the hepatic drug-metabolizing system. In addition, tolerance develops in the serotonergic neuronal system while supersensitivity develops in the dopaminergic neuronal system. Biochemical findings suggest that increased mesolimbic dopaminergic neuronal function plays an important role in the development of the supersensitivity.
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Dopamine was measured by microdialysis in the nucleus accumbens of freely moving rats while they experienced rewarding food, brain stimulation and drugs. Extracellular dopamine increased 37% when the animals pressed a lever for food reward. Electrical stimulation of a lateral hypothalamic feeding-reward (self-stimulation) site caused a similar increase in dopamine, with or without food. At the site in the nucleus accumbens where rats will administer amphetamine to themselves, injections of amphetamine or cocaine increased extracellular dopamine five-fold. Thus amphetamine and cocaine increase dopamine in a behavior reinforcement system which is normally activated by eating. Conversely, the release of dopamine by eating could be a factor in addiction to food.
Article
Two experiments were conducted to examine the effects of pimozide on cocaine-produced conditioning to a specific environmental context. On 8 treatment days, 12 rats were injected with cocaine (10 mg/kg i.p.) and 12 with saline prior to placement for 60 min into a test chamber outfitted with infrared emitters and detectors. Following each treatment session the saline group received cocaine in their home-cages and the cocaine group received saline. Cocaine produced a significant increase in vertical activity on treatment days. On test days all rats received saline. Significantly greater vertical activity was observed in the group previously receiving cocaine in the test environment. All rats than received 8 more treatment sessions. On saline test days, primozide (0.4 mg/kg i.p.) pretreatment failed to antagonize expression of the conditioned effect. In experiment 2, pimozide was given prior to treatment and no evidence of conditioning was seen on saline test days. Thus, pimozide blocked the establishment but not the expression of cocaine-produced environment-specific conditioning. These results suggest that during conditioning, the effects of cocaine on dopaminergic neurons may have produced a change that subsequently influenced behaviour even when dopaminergic systems were blocked.
Article
Animals that eat and/or drink in response to electrical stimulation of the lateral hypothalamus (ESLH-pos) are more responsive to both schedule-induced polydipsia (SIP) tests and a series of amphetamine (AMPH) injections than animals that do not exhibit these behaviors (ESLH-neg). Moreover, prior exposure to the behaviorally activating SIP experience, or to AMPH, permanently transformed the ESLH-neg animals into animals that reliably ate or drank during ESLH. Prior treatment with AMPH also increases the water consumed during subsequent SIP tests. Thus, initial of induced differences in sensitivity to activating experiences can determine behavioral propensities.
Article
The discovery that the brain contains neurons utilizing dopamine (DA) as their transmitter has led to studies of the behavioral function of these neurons. Changes in overall level of activity of DA neurons appear to produce parallel changes in locomotor activity. Additionally, DA neurons seem to mediate in part the effects of biologically significant (reinforcing) stimuli on learning. One way in which reinforcing stimuli produce learning is to increase the incentive motivational (response-eliciting) properties of neutral stimuli associated with them; also, reinforcing stimuli maintain the incentive motivational properties of previously conditioned incentive stimuli. Normal DA functioning appears to be required for the establishment and maintenance of incentive learning in naive animals. Previous incentive learning in trained animals can influence behavior for a time even when the function of DA neurons is disrupted; however, with continued testing in the absence of normal DA functioning, previously established conditioned incentive stimuli cease to influence behavior. From these observations and recent physiological, anatomical and biochemical studies of DA systems it is suggested that the biological substrate of DA-mediated incentive learning is a heterosynaptic facilitation of muscarinic cholinergic synapses. This model has important clinical implications since it has been suggested that DA hyperfunctioning underlies the development of schizophrenia.
Article
Behavioral and neurochemical cross-sensitization between cocaine and stress was examined. The effects of stress and cocaine on extracellular levels of dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were measured by in vivo microdialysis in the rostral ventral striatum, including the nucleus accumbens. Pretreatment with a daily 20 min footshock stress (0.45 mA/200 ms/s) for 5 days enhanced the cocaine-induced increase in extracellular dopamine levels in shock compared to sham shock-pretreated rats. The motor stimulant response to acute cocaine was also augmented in shock-pretreated rats. There was a slight but significant decrease in the levels of DOPAC and HVA in both groups following cocaine but no differences between shock and sham shock animals. In contrast, in the converse experiment, pretreatment with daily cocaine (15 mg/kg, i.p.) for 5 days did not significantly alter the stress-induced levels of extracellular dopamine compared to controls. The levels of DOPAC and HVA were not different between cocaine- and saline-pretreated groups although there was a trend towards enhanced metabolite levels in cocaine-pretreated animals. These data in part support a role for enhanced dopamine neurotransmission in mediating behavioral cross-sensitization between psychostimulants and stress.
Article
Pretreatment of B6AF1/J mice with d-amphetamine HCl 10 mg/kg, twice daily for 5 days, produced a 4-fold increase in the running response to a test dose of 5 mg/kg amphetamine. Amphetamine pretreatment decreased whole-brain norepinephrine levels to 50% of control values and whole-brain dopamine to 85%. The test dose of 5 mg/kg amphetamine lowered whole brain norepinephrine levels of control mice from 0.50 mug/g to 0.28 mug/g in 2 h. In amphetamine-pretreated mice, this injection caused an increase in whole-brain norepinephrine levels from 0.22 mug/g to 0.55 mug/g at 30 min, followed by a decrease to 0.22 mug/g at 60 min. No change in whole brain dopamine levels was observed in either group. Amphetamine sensitization and norepinephrine depletion were still evident 25 days after pretreatment. No cross sensitization to morphine or cocaine was observed. Reserpine pretreatment resulted in a 3-fold increase in locomotor activity following injection of d-amphetamine, 5 mg/kg. No sensitization or changes in catecholamine levels were observed in amphetamine-treated A/J mice. These results suggest that the sensitization produced by amphetamine pretreatment may be related to the depletion of brain norepinephrine.
Article
Psychotropic drugs such as methadone, morphine and bulbocapnine produce increments in dopamine metabolism as an unconditioned reflex. When a buzzer noise is used as a conditioned stimulus (CS) with these drugs as unconditioned stimuli, the buzzer CS acquires the properties of the drugs in increasing dopamine metabolism. These results suggest that the brain, like other visceral organs, can be conditioned in terms of neurotransmitter release or metabolism.
Article
Six subjects were given the opportunity to work for saline placebo and hydromorphone (4 mg i.v.) several times weekly before and during a period of maintenance on methadone (100 mg p.o. daily). Measures of pupillary change and reports of "liking" in response to hydromorphone dropped to saline control levels when the daily dose of methadone was approximately 60 mg. Half of the subjects continued to work intermittently for hydromorphone for four weeks while they were receiving 100 mg of methadone daily. These data support the assumption that methadone maintenance reduces the reinforcement value of other opiates and behaviors associated with obtaining them.
Article
It is said that amphetamine induces stereotypy and locomotion in rats; however, the present paper shows amphetamine-induced stereotyped locomotion by analyzing the route of locomotion in an open field. Details of the analysis are given, normal as well as stereotypic features are discerned, and the results are discussed in relation to contemporary views on locomotion and exploration and on the mechanisms of amphetamine effect.
Article
The running response of B6AF1/J mice to 25 mg/kg of morphine sulfate was increased up to 3-fold when this dose was administered either twice daily for 5 days or once a week for 2 or 3 weeks. The effect of weekly pretreatment was proportional to the dose of morphine and lasted as long as 1 month after pretreatment was stopped. There was no sensitization when the mice were less than 15 days old at the time of pretreatment. Of the parental strains, untreated C57Bl/6J mice showed a good running response to morphine, while A/J mice showed little response. Pretreatment of either of these strains produced only slight sensitization. Pretreatment of the hybrids with levorphanol increased the response to morphine. Dextrorphan and naloxone were ineffective. Sensitization by morphine was blocked by naloxone. Increased morphine running was not associated with analgesic tolerance as measured by the tail-flick assay. Morphine pretreatment produced some increase in the running response to amphetamine and to cocaine. Pretreatment with amphetamine or cocaine did not increase the response to morphine.
Article
Repeated administration of cocaine to B6AF1/J mice increased their running response to 20 mg/kg cocaine as much as four-fold over the response to the first injection. After four daily injections, the extent of the increase was proportional to the dose of cocaine that was used for pretreatment. Sensitization persisted for as long as 2 months after the last injection of cocaine. Cocaine-pretreated mice did not show an increased running response to either morphine or d-amphetamine. The response to cocaine was increased two-fold by treatment with morphine and three-fold by pretreatment with d-amphetamine. Pretreatment with either imipramine or reserpine did not produce sensitization to cocaine. There was no correlation between cocaine sensitization and whole-brain catecholamine levels. There were marked differences in both the running response to cocaine and the extent of cocaine sensitization betwee the parental strains, C57B1/6J and A/J. Experiments with recombinant-inbred lines, derived from C57B1/6By and BALB/cBy mice, suggest that the initial response to cocaine and the development of sensitization are controlled by different genetic determinants.
Article
Facial expressions, whether innate or acquired, are one of the richest nonverbal communicational catalogs of man. This chapter shows facial expressions in the experimental part of the discussion and illustrates the three prototypes of facial play described by Darwin as that of “good spirit,” of “contempt,” and of “low spirit or disgust.” Darwin intended to describe facial expressions used by man to reflect his feelings, his mood, and his spirit. The expressions demonstrated in the chapter are by no means acquired; they are present at the date of birth, perhaps even earlier, and are elicitable by different chemical stimuli. The hedonically different meaning of the sweet and the bitter and the hedonically polar value of odors of fresh and good food and that of rotten one, unlock facial expressions identical to those indicating “high and low spirits.” The individual first exposed to typical stimulants of “good” and “bad” food-related chemical cues evaluates these signals at low levels of the central nervous system.
Article
The effect of local application of morphine (5 microgram) into the ventral tegmental area (VTA) or substantia nigra, pars compacta (SNc) on spontaneous activity was studied in the rat. Morphine in the VTA but not SNc produced an enhancement of locomotor activity which became progressively augmented with repeated injections. This effect could be blocked by systemic injections of naloxone or haloperidol. It is suggested that stimulation of opiate receptors in the vicinity of dopamine cell bodies can increase the activity of ascending mesencephalic dopamine neurones.
Article
The chronic administration of phenylethylamine (50 mg/kg) or d-amphetamine (3.75 mg/kg) produces stereotyped behavior in rats. This chronic administration induces a behavioral sensitization consisting of an increase in intensity of stereotypies and a decrease in their latency to onset. The substitution of phenylethylamine for d-amphetamine, or vice versa, maintains not only stereotypies but also the sensitization effect. Acute pretreatments with the anti-psychotic dopamine blockers haloperidol and pimozide block stereotypy induced by both phenylethylamine and d-amphetamine, whereas antipsychotics with fewer extrapyramidal effects, thioridazine and clozapine, preferentially block phenylethylamine-evoked behavior. The fact that stereotypy induced by phenylethylamine, unlike that induced by d-amphetamine, does not depend so greatly upon neostriatal actions suggests that it may therefore represent a better animal model for schizophrenia.
Article
One or two bottle preference tests, i.e., relative fluid consumption, constitute the primary methodology for determining acceptance or rejection of tastes in animals other than humans. These tests require organisms to initiate and maintain drinking behavior, and, therefore, can not be applied to preparations which do not eat or drink spontaneously. The taste reactivity test, a new method for assessing responses to gustatory stimuli, circumvents this shortcoming. A 50 microliter taste stimulus is injected directly into the oral cavity of a freely moving rat and the immediate response videotaped for frame by frame analysis. Each of the sapid stimuli used (4 concentrations of sucrose, NaCl, HCl, and quinine HCl) generated a stereotyped response derived from a lexicon of 4 mimetic (movements of lingual, masticatory, and facial musculature) and 5 body response components. Responses to taste stimuli were highly consistent within and between rats. For example, sapid sucrose, NaCl and HCl stimuli elicited a response sequence beginning with low amplitude, rhythmic mouth movements, followed by rhythmic tongue protrusions, and then lateral tongue movements. No body movements accompanied these mimetic responses. In contrast, quinine in concentrations at and above 3 X 10(-5) M (1/2 log step above the absolute behavioral threshold for quinine) elicited a response pattern beginning with gaping and proceeding through as many as 5 body responses. These normative data for the intact rat can be directly compared to the taste reactivity of neurally ablated preparations which do not spontaneously feed or drink. Such comparisons can be utlized in determining the neural substrates necessary for the execution and regulation of ingestive behavior.
Article
The author describes an orderly progression of clinical syndromes (euphoria, dysphoria, paranoid psychosis) with cocaine use that is related to dosage, chronicity, and genetic and experiential predispositions. That affective alternations are caused by a drug which also produces a schizophreniform psychosis suggests a continuum with implications for understanding the endogenous psychoses. The author emphasizes that alternations in the same neurotransmitter substances may be involved in these multiple psychiatric syndromes, which contrasts with previous "one illness, one transmitter" models.
Article
The injection of morphine sulfate into baby mice twice daily for 5 days increased their running reaponse to morphine when they were tested as adults. If treatment was completed before the mice were )5 days old there was no effect. Sensitization to morphine running was longer-lasting than either analgesic tolerance or tolerance to morphine running may be a form of denervation hypersensitivity that has several features in common with noise-induced sensitization to audiogenic seizures.
Article
We examined the effect of chronic nicotine treatment on dopaminergic activity by measuring the effects of D1 and D2 dopamine (DA) receptor agonists and antagonists on tritium release from mouse striatum preloaded with [3H]DA. The radioactivity released during superfusion was separated on alumina columns and the distribution and efflux of [3H]DA and its main 3H-labeled metabolites were quantified. After preloading by incubation with [3H]DA, the electrical stimulation-evoked tritium overflow was higher in striatum prepared from nicotine-treated mice, whereas in vitro addition of nicotine caused a similar increase in tritium release from striatum of untreated and chronic nicotine-treated mice. The overflow of [3H]DA and its 3H-metabolites exhibited similar distribution patterns in [3H]DA-preloaded striatum dissected from untreated and chronic nicotine-pretreated mice, indicating that repeated injections with nicotine did not alter the metabolism of [3H]DA taken up by the tissue. (-)-Quinpirole, a selective agonist for D2 DA receptors, and apomorphine, a nonselective D1/D2 agonist, inhibited the electrical stimulation-induced tritium efflux from striatum of untreated mice, whereas (+/-)-sulpiride, a D2 DA receptor antagonist, enhanced the evoked release of tritium. These changes in tritium efflux effected by (-)-quinpirole and (+/-)-sulpiride reflected changes in [3H]DA release and not in DA metabolism, as shown by separation of the released radioactivity on alumina columns. The D1 receptor agonist (+/-)-SKF-38393 did not affect the tritium overflow, whereas the D1 receptor antagonist (+)-SCH-23390 exerted a stimulatory action but only at a high concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
Recent evidence suggests that repeated stimulation of D1 dopamine receptors within the rat striatum leads to an enhancement of both D1 and D2 dopamine receptor-mediated responses. The present study used both behavioral observations and extracellular single unit recording techniques to investigate this phenomenon following repeated administration of selective D1 dopamine receptor agonists. Groups of rats received twice daily administration of either saline or the partial D1 dopamine receptor agonist SKF 38393 (8 mg/kg, s.c.) for three weeks. Rats were tolerant to the ability of SKF 38393 to enhance grooming behavior when tested immediately following the last of the 42 treatment injections. However, the ability of this last SKF 38393 injection to potentiate oral stereotyped behavior following administration of the D2 DA agonist quinpirole was still evident. Following a one-day withdrawal, grooming responses to SKF 38393 had returned to normal. At this time, administration of quinpirole, without concomitant SKF 38393, failed to significantly promote oral stereotypies, as is typical of normal rats. Following a one-week withdrawal period, SKF 38393-induced grooming behavior was significantly enhanced and quinpirole, administered without SKF 38393, produced pronounced oral stereotyped behavior in 10 of 12 rats tested. Following a one-month withdrawal, these sensitized responses were no longer evident. Single-cell recordings from rat lateral striatal neurons revealed similar time-dependent alterations in the effects of iontophor