Article

Altered reward sensitivity to sucrose outcomes prior to drug exposure in alcohol preferring rats

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

Addiction involves key impairments in reward sensitivity (RS). The current study explored impaired RS to natural reward as a predisposing factor to addictive-like behavior. Alcohol preferring (P) rats are selectively bred based on significantly greater ethanol consumption and preference and offer the ability to inspect differences in subjects with a positive family history of addictive-like behavior. P rat’s RS was compared to RS in the well-used Sprague-Dawley (SD) strain. To assess RS in a novel manner, instrumental incentive contrast, discrimination and consumption of sucrose solution were examined. Animals performed in a free operant situation for different sucrose concentration solutions using a block of ‘mixed’ trials with alternating outcome concentrations (e.g., 5 and 10 % sucrose) to change outcome value in a predictable manner. Animals also performed for reward in blocks of single outcome trials (5 or 10 or 20 or 40 % sucrose daily exposure) surrounding the mixed block. RS (e. g., reward discrimination and contrast effects between and within-sessions) was measured by changes in trials completed, instrumental response latency and consumption. P rats expressed an altered profile of RS with a greater tendency toward equivalent responding to different outcomes within the same session and an absence of incentive contrast from diverse reward comparisons. In contrast, SD animals expressed within-session reward discrimination and a subset of incentive contrast effects. These effects were moderated by food deprivation more consistently in SD compared to P rats. P rat alterations in processing natural rewards could predispose them to addictive-like behaviors including greater alcohol consumption and preference.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... While displaying similar preshift behavior, postshift behavior revealed that P required 3 days to "recover" and consume similar amounts of 4% sucrose as their unshifted control group. This is in opposition to McGraw et al. (2024), which recently found no contrast effect in P rats. HAD rats overall recovered from contrast after just 1 day. ...
... Recent results have shown that while food restriction in Sprague-Dawley rats may enhance sucrose motivation and consumption, nonrestricted P rats will still consume significant amounts of high sucrose concentrations. Future work could attempt to use free-fed P rats, particularly when utilizing ethanol(McGraw et al., 2024). ...
Article
Full-text available
Background The loss of a job or relationship are a couple of examples of unexpected reward loss. Life events, such as these can induce negative emotional reactions (e.g., anxiety and stress), which have been associated with increased alcohol consumption and in turn, an increased risk of developing an alcohol use disorder (AUD). The present study analyzed consummatory successive negative contrast (SNC) for the first time in alcohol preferring (P) and high alcohol drinking (HAD) rats that have been selectively bred to consume high amounts of ethanol. Following reward loss, animals were given free access to ethanol to determine whether consumption would increase as a possible indication of any negative emotional reaction. Methods Male and female P and HAD rats were split into shifted and unshifted groups receiving either 32% or 4% sucrose for 5 min across 10 preshift days. Subsequently, all animals received 4% sucrose for four postshift days, across which, animals were given access to 20% ethanol for 30 min after access to 4% sucrose. Results Male and female P rats demonstrated a longer contrast effect than HAD rats, indicated by a longer recovery time following the downshift in reward. Conversely, HAD males did not demonstrate a contrast effect following this downshift in reward unlike their female counterparts. Surprisingly, P rats who experienced a loss of reward consumed significantly less ethanol than animals who did not. Lastly, individual measure of contrast size, or shift ratio, was significantly associated with greater ethanol consumption in HAD males only, who did not display a contrast effect. Conclusions These data indicate different reactivity to SNC between these two lines and sexes, suggesting different genetic and sex‐related mechanisms underlying sensitivity to an unexpected loss of reward and ethanol consumption following this loss.
Article
Full-text available
Rats shifted from a high to a low concentration of sucrose make fewer licks for the low concentration than rats that experience only the low concentration of sucrose. This phenomenon, referred to as successive negative contrast, is eliminated after bilateral electrolytic lesions of the amygdala. Because the amygdala receives direct projections from the gustatory zone of the parabrachial nuclei of the pons (PBN), this experiment was designed to examine this phenomenon in rats with electrophysiologically guided bilateral electrolytic lesions of the PBN. The results of this experiment showed that lesions of the PBN fully prevent contrast in rats shifted from the high to the low concentration of sucrose. Thus, an intact PBN is essential for the occurrence of successive negative contrast effects in rats.
Article
Full-text available
Contrast effects were obtained in rats in the consumption of saccharin solutions in three different paradigms. Degree of negative contrast varied as a function of concentration disparity, but not equally in the three procedures. Successive negative contrast occurred following shifts from 0.15% to either 0.075% or 0.05% saccharin but did not occur following shifts to 0.10% or 0.125% saccharin. Some degree of simultaneous contrast was obtained with all four concentration disparities. Anticipatory contrast, where the intake of the first substance is suppressed by a more preferred second substance, occurred only in the case of the 0.05%–0.15% difference in concentrations. It was suggested that the several contrast paradigms engage somewhat different psychological processes differentially involving emotional, sensory, and associative mechanisms, but all lead to behavior based on relative value. A modification of Toates's (1981) incentive model of ingestive behavior was suggested to incorporate relativity effects based on both associative and nonassociative factors in the consumption of both nutritive and nonnutritive substances.
Article
Full-text available
Behavioral strategies are often classified based on whether reinforcer value controls reinforcement. Value-sensitive behaviors, in which animals update their actions when reinforcer value is changed, are classified as goal-directed; conversely, value-insensitive actions, where behavior remains consistent when the reinforcer is removed or devalued, are considered habitual. Basic reinforcement schedules can help to bias behavior toward either process: random ratio (RR) schedules are thought to promote the formation of goal-directed behaviors while random intervals (RIs) promote habitual control. However, how the schedule-specific features of these tasks interact with other factors that influence learning to control behavior has not been well characterized. Using male and female mice, we asked how distinct food restriction levels, a strategy often used to increase task engagement, interact with RR and RI schedules to control performance during task acquisition and devaluation procedures. We determined that food restriction level has a stronger effect on the behavior of mice following RR schedules compared with RI schedules, and that it promotes a decrease in response rate during devaluation procedures that is best explained by the effects of extinction rather than devaluation. Surprisingly, food restriction accelerated the decrease in response rates observed following devaluation across sequential extinction sessions, but not within a single session. Our results support the idea that the relationships between schedules and behavioral control strategies are not clear-cut and suggest that an animal’s engagement in a task must be accounted for, together with the structure of reinforcement schedules, to appropriately interpret the cognitive underpinnings of behavior.
Preprint
Full-text available
The past decades have seen tremendous progress in fundamental studies on economic choice in humans. However, elucidation of the underlying neuronal processes requires invasive neurophysiological studies that are met with difficulties in humans. Monkeys as evolutionary closest relatives offer a solution. The animals display sophisticated and well-controllable behavior that allows to implement key constructs of proven economic choice theories. However, the similarity of economic choice between the two species has never been systematically investigated. We investigated compliance with the independence axiom (IA) of expected utility theory as one of the most demanding choice tests and compared IA violations between humans and monkeys. Using generalized linear modeling and cumulative prospect theory (CPT), we found that humans and monkeys made comparable risky choices, although their subjective values (utilities) differed. These results suggest similar fundamental choice mechanism across these primate species and encourage to study their underlying neurophysiological mechanisms.
Article
Full-text available
Animal models of substance use disorders have been criticized for their limited translation. One important factor behind seeking and taking that has so far been largely overlooked is the availability of alternative non-drug rewards. We recently reported that only about 15% of outbred Wistar rats will choose alcohol over a sweet solution of saccharin. It was also shown using a novel operant model of choice of drugs over social rewards that social interaction consistently attenuates self-administration and incubation of craving for stimulants and opioids. Whether this is also true for alcohol and choice of alcohol over a sweet reward translates to social rewards is currently unknown. We therefore evaluated choice between alcohol and a social reward in different experimental settings in both male and female Wistar rats. We found, in contrast to prior work that employed discrete choice of drugs vs. social reward, that rats almost exclusively prefer alcohol over social interaction, irrespective of the nature of the social partner (cagemate vs. novel rat), the length of interaction, housing conditions and sex. Alcohol choice was reduced when the response requirement for alcohol was increased. However, rats persisted in choosing alcohol, even when the effort required to obtain it was 10–16 times higher (for females and males respectively) than the one for the social reward. Altogether, these results indicate that the social choice model may not generalize to alcohol, pointing to the possibility that specific interactions between alcohol and social reward, not seen when a sweet solution is used as an alternative to the drug, may play a crucial role in alcohol vs. social choice experiments.
Article
Full-text available
Addiction is a complex disease that impacts millions of people around the world. Clinically, addiction is formalized as substance use disorder (SUD), with three primary symptom categories: exaggerated substance use, social or lifestyle impairment, and risky substance use. Considerable efforts have been made to model features of these criteria in non-human animal research subjects, for insight into the underlying neurobiological mechanisms. Here we review evidence from rodent models of SUD-inspired criteria, focusing on the role of the striatal dopamine system. We identify distinct mesostriatal and nigrostriatal dopamine circuit functions in behavioral outcomes that are relevant to addictions and SUDs. This work suggests that striatal dopamine is essential for not only positive symptom features of SUDs, such as elevated intake and craving, but also for impairments in decision making that underlie compulsive behavior, reduced sociality, and risk taking. Understanding the functional heterogeneity of the dopamine system and related networks can offer insight into this complex symptomatology and may lead to more targeted treatments.
Article
Full-text available
A consistent preclinical finding is that exposure to alcohol during adolescence produces a persistent hyperdopaminergic state during adulthood. The current experiments determine that effects of Adolescent Intermittent Ethanol (AIE) on the adult neurochemical response to EtOH administered directly into the mesolimbic dopamine system, alterations in dendritic spine and gene expression within the nucleus accumbens shell (AcbSh), and if treatment with the HDACII inhibitor TSA could normalize the consequences of AIE. Rats were exposed to the AIE (4 g/kg ig; 3 days a week) or water (CON) during adolescence, and all testing occurred during adulthood. CON and AIE rats were microinjected with EtOH directly into the posterior VTA and dopamine and glutamate levels were recorded in the AcbSh. Separate groups of AIE and CON rats were sacrificed during adulthood and Taqman arrays and dendritic spine morphology assessments were performed. The data indicated that exposure to AIE resulted in a significant leftward and upward shift in the dose-response curve for an increase in dopamine in the AcbSh following EtOH microinjection into the posterior VTA. Taqman array indicated that AIE exposure affected the expression of target genes (Chrna7, Impact, Chrna5). The data indicated no alterations in dendritic spine morphology in the AcbSh or any alteration in AIE effects by TSA administration. Binge-like EtOH exposure during adolescence enhances the response to acute ethanol challenge in adulthood, demonstrating that AIE produces a hyperdopaminergic mesolimbic system in both male and female Wistar rats. The neuroadaptations induced by AIE in the AcbSh could be part of the biological basis of the observed negative consequences of adolescent binge-like alcohol exposure on adult drug self-administration behaviors.
Article
Full-text available
Decisions can be risky or riskless, depending on the outcomes of the choice. Expected utility theory describes risky choices as a utility maximization process: we choose the option with the highest subjective value (utility), which we compute considering both the option’s value and its associated risk. According to the random utility maximization framework, riskless choices could also be based on a utility measure. Neuronal mechanisms of utility-based choice may thus be common to both risky and riskless choices. This assumption would require the existence of a utility function that accounts for both risky and riskless decisions. Here, we investigated whether the choice behavior of two macaque monkeys in risky and riskless decisions could be described by a common underlying utility function. We found that the utility functions elicited in the two choice scenarios were different from each other, even after taking into account the contribution of subjective probability weighting. Our results suggest that distinct utility representations exist for risky and riskless choices, which could reflect distinct neuronal representations of the utility quantities, or distinct brain mechanisms for risky and riskless choices. The different utility functions should be taken into account in neuronal investigations of utility-based choice.
Article
Full-text available
Behavioural economic theories of addiction contend that greater expected value of drug relative to alternative non-drug rewards is the core mechanism underpinning vulnerability to and recovery from addiction. To evaluate this claim, we exhaustively review studies with human drug users that have measured concurrent choice between drugs vs. alternative rewards, and explored individual differences. These studies show that drug choice can be modulated by drug cues, drug devaluation, imposition of costs/punishment and negative mood induction. Regarding individual differences, dependence severity was reliably associated with overall drug preference, and self-reported drug use to cope with negative affect was reliably associated with greater sensitivity to mood induced increases in drug choice. By contrast, there were no reliable individual differences in sensitivity to the effect of drug cues, drug devaluation or punishment on drug choice. These findings provide insight into the mechanisms that underpin vulnerability to dependence: vulnerability is conferred by greater relative value ascribed to drugs, and relative drug value is further augmented by negative affective states in those who report drug use coping motives. However, dependence does not appear to be characterised by abnormal cue-reactivity, habit learning or compulsion. We then briefly review emerging literature which demonstrates that therapeutic interventions and recovery from addiction might be attributed to changes in the expected relative value of drug versus alternative rewards. Finally, we outline a speculative computational account of the distortions in decision-making that precede action selection in addiction, and we explain how this account provides a blueprint for future research on the determinants of drug choice, and mechanisms of treatment and recovery from addiction. We conclude that a unified economic decision-making account of addiction has great promise in reconciling diverse addiction theories, and neuropsychological evaluation of the underlying decision mechanisms is a fruitful area for future research and treatment.
Article
Full-text available
Contemporary theories of instrumental performance assume that responding can be controlled by 2 behavioral systems, 1 goal-directed that encodes the outcome of an action, and 1 habitual that reinforces the response strength of the same action. Here we present a model of free-operant behavior in which goal-directed control is determined by the correlation between the rates of the action and the outcome whereas the total prediction error generated by contiguous reinforcement by the outcome controls habitual response strength. The outputs of these two systems summate to generate a total response strength. This cooperative model addresses the difference in the behavioral impact of ratio and interval schedules, the transition from goal-directed to habitual control with extended training, the persistence of goal-directed control under choice procedures and following extinction, among other phenomena. In these respects, this dual-system model is unique in its account of free-operant behavior. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
Article
Full-text available
As a part of a larger Affectome Project (http://neuroqualia.org/background.php) with an overarching goal of mapping and redefining biological substrates of feelings and emotions, we explored the neural underpinnings for the functions of motivation and emotion. Historically emotion and motivation have been placed into distinct neural circuits and examined separately. We propose a novel view of significant neural convergence of emotion and motivation, in contrast to conventional neural-based frameworks emphasizing segregation. Evidence from diverse research areas in emotion and motivation was reviewed, pinpointing key neural regions of overlap. The findings support important neural sharing between emotion and motivation, suggesting that these two functions are tightly intertwined with one another in the brain. Neural overlap does not necessarily imply continuous functional overlap. Even if identical brain regions/systems are activated for motivation and emotion, this activation may involve distinct and unique patterns of connection and information flow as the network shifts functionality. This review highlights the crucial importance of further research to explicate the patterns and modes of responding of these overlapping systems.
Article
Full-text available
Background A significant component of ethanol (EtOH) dependence is the disruption to decision‐making processes. Prior work has shown EtOH dependence biases habitual seeking of EtOH and disrupts neural mechanisms supporting decision‐making. This has contributed to the hypothesis that habitual EtOH seeking in EtOH dependence may promote excessive habitual or compulsive EtOH consumption. However, decision‐making and behavioral processes underlying seeking and consummatory behaviors differ. Here, we examine the microstructure of EtOH consummatory behavior in the context of habitual EtOH seeking. Methods Following home cage pre‐exposure to EtOH, C57Bl/6J mice underwent 4 rounds of chronic intermittent EtOH (CIE) or air exposure. Following acute withdrawal, mice began training for operant self‐administration of 15% EtOH. Training consisted of 16‐hour sessions in which mice were trained in a random ratio (RR) schedule of reinforcement for 30‐second access to the EtOH sipper. To test for CIE‐induced changes in action control, we used sensory‐specific satiation and assessed the effect of outcome devaluation on EtOH seeking. Importantly, the use of a lickometer during operant training allowed us to measure the microstructure of lick behavior. Results Prior induction of EtOH dependence led to increased EtOH seeking, consumption, and an insensitivity to outcome devaluation, the latter indicative of habitual EtOH seeking. We also found altered consummatory lick patterns in CIE‐exposed mice compared to Air controls. While CIE mice had significantly more licks in a burst and a longer burst duration, there were no differences in the total number of bursts compared to Air controls. Furthermore, these EtOH consummatory behaviors correlated with blood EtOH concentrations (BECs), while EtOH‐seeking responses did not. Conclusions Our results confirm that EtOH dependence can produce habitual EtOH seeking and suggests the increased EtOH consummatory behaviors following EtOH dependence are separable from decision‐making processes controlling EtOH seeking.
Article
Full-text available
Rationale: Drug reward plays a central role in acquiring drug-seeking behavior. However, subjects may continue using drugs despite negative consequences because self-administration becomes habitual, and divorced from outcome values. Although a history of drug and alcohol use expedite habit acquisition, and in spite of the fact that self-administration leads to intoxication, the acute effects of drugs on habitual responding are not well understood. Objectives: We sought to observe how acute ethanol and amphetamine affect the balance between habitual and goal-directed behavior, as measured by a fluid-reinforced operant conditioning task. Methods: Selectively bred crossed high-alcohol-preferring (cHAP) mice were trained on an operant conditioning task reinforced on a variable interval schedule with 1% banana solution, which was subsequently devalued via LiCl pairing in half the animals. Ethanol (1.0 g/kg), amphetamine (2.0 mg/kg), or saline was administered prior to a post-devaluation test. Results: Overall, mice showed habitual behavior, but when divided into high- or low-responding groups based on training response rates, saline-treated, low-responding animals devalued, while saline-treated high-responding animals did not. Furthermore, amphetamine elicited devaluation even in high-responding animals, while ethanol prevented devaluation even in low-responding animals. Conclusions: These data show that ethanol shifts animals toward behaving habitually. This may illuminate why alcohol-intoxicated individuals display impaired judgment about the relative merits of drinking, and potentially serve as a mechanism by which intoxicated subjects resume previously devalued behaviors, such as comorbid drug use. These findings also show that high variable interval response rates facilitate a shift from goal-directed to habitual behavior.
Article
Full-text available
In the present study we used a diet enriched with 10% sucrose, which was consumed by adolescent animals of the experimental group for one month. We found that consumption of sweet food during sexual maturation affected alcohol preference, anxiety, and locomotor and exploratory activity in the adult rats. Our data show that easily available tasty food during adolescence probably impairs the reward system and serves as a trigger of future alcohol preference.
Article
Full-text available
Many of the neurocircuits and hormones known to underlie the sensations of hunger and satiety also substantially alter the activity of the dopaminergic reward system. Much interest lies in the ways that hunger, satiety, and reward tie together, as the epidemic of obesity seems tied to the recent development and mass availability of highly palatable foods. In this review, we will first discuss the basic neurocircuitry of the midbrain and basal forebrain reward system. We will elaborate how several important mediators of hunger—the agouti-related protein neurons of the arcuate nucleus, the lateral hypothalamic nucleus, and ghrelin—enhance the sensitivity of the dopaminergic reward system. Then, we will elaborate how mediators of satiety—the nucleus tractus solitarius, pro-opiomelanocortin neurons of the arcuate nucleus, and its peripheral hormonal influences such as leptin—reduce the reward system sensitivity. We hope to provide a template by which future research may identify the ways in which highly rewarding foods bypass this balanced system to produce excessive food consumption.
Article
Full-text available
Increasing evidence supports the hypothesis that impulsive decision-making is a heritable risk factor for an alcohol use disorder (AUD). Clearly identifying a link between impulsivity and AUD risk, however, is complicated by the fact that both AUDs and impulsivity are heterogeneous constructs. Understanding the link between the two requires identifying the underlying cognitive factors that lead to impulsive choices. Rodent models have established that a family history of excessive drinking can lead to the expression of a transgenerational impulsive phenotype, suggesting heritable alterations in the decision-making process. In the present study, we explored the cognitive processes underlying impulsive choice in a validated, selectively bred rodent model of excessive drinking—the alcohol-preferring (“P”) rat. Impulsivity was measured via delay discounting (DD), and P rats exhibited an impulsive phenotype as compared to their outbred foundation strain—Wistar rats. Steeper discounting in P rats was associated with a lack of a prospective behavioral strategy, which was observed in Wistar rats and was directly related to DD. To further explore the underlying cognitive factors mediating these observations, a drift diffusion model of DD was constructed. These simulations supported the hypothesis that prospective memory of the delayed reward guided choice decisions, slowed discounting, and optimized the fit of the model to the experimental data. Collectively, these data suggest that a deficit in forming or maintaining a prospective behavioral plan is a critical intermediary to delaying reward, and by extension, may underlie the inability to delay reward in those with increased AUD risk.
Article
Full-text available
Rewards are both “liked” and “wanted,” and those 2 words seem almost interchangeable. However, the brain circuitry that mediates the psychological process of “wanting” a particular reward is dissociable from circuitry that mediates the degree to which it is “liked.” Incentive salience or “wanting,” a form of motivation, is generated by large and robust neural systems that include mesolimbic dopamine. By comparison, “liking,” or the actual pleasurable impact of reward consumption, is mediated by smaller and fragile neural systems, and is not dependent on dopamine. The incentive-sensitization theory posits the essence of drug addiction to be excessive amplification specifically of psychological “wanting,” especially triggered by cues, without necessarily an amplification of “liking.” This is because of long-lasting changes in dopamine-related motivation systems of susceptible individuals, called “neural sensitization.” A quarter-century after its proposal, evidence has continued to grow in support the incentive-sensitization theory. Further, its scope is now expanding to include diverse behavioral addictions and other psychopathologies.
Article
Full-text available
The striatum is a key brain region involved in reward processing. Striatal activity has been linked to encoding reward magnitude and integrating diverse reward outcome information. Recent work has supported the involvement of striatum in the valuation of outcomes. The present work extends this idea by examining striatal activity during dynamic shifts in value that include different levels and directions of magnitude disparity. A novel task was used to produce diverse relative reward effects on a chain of instrumental action. Rats (Rattus norvegicus) were trained to respond to cues associated with specific outcomes varying by food pellet magnitude. Animals were exposed to single-outcome sessions followed by mixed-outcome sessions, and neural activity was compared among identical outcome trials from the different behavioral contexts. Results recording striatal activity show that neural responses to different task elements reflect incentive contrast as well as other relative effects that involve generalization between outcomes or possible influences of outcome variety. The activity that was most prevalent was linked to food consumption and post-food consumption periods. Relative encoding was sensitive to magnitude disparity. A within-session analysis showed strong contrast effects that were dependent upon the outcome received in the immediately preceding trial. Significantly higher numbers of responses were found in ventral striatum linked to relative outcome effects. Our results support the idea that relative value can incorporate diverse relationships, including comparisons from specific individual outcomes to general behavioral contexts. The striatum contains these diverse relative processes, possibly enabling both a higher information yield concerning value shifts and a greater behavioral flexibility.
Article
Full-text available
Choice behavior combines discrimination between distinctive outcomes, preference for specific outcomes and relative valuation of comparable outcomes. Previous work has focused on 1 component (i.e., preference) disregarding other influential processes that might provide a more complete understanding. Animal models of choice have been explored primarily utilizing extensive training, limited freedom for multiple decisions and sparse behavioral measures constrained to a single phase of motivated action. The present study used a paradigm that combines different elements of previous methods with the goal to distinguish among components of choice and explore how well components match predictions based on risk-sensitive foraging strategies. In order to analyze discrimination and relative valuation, it was necessary to have an option that shifted and an option that remained constant. Shifting outcomes among weeks included a change in single-option outcome (0 to 1 to 2 pellets) or a change in mixed-option outcome (0 or 5 to 0 or 3 to 0 or 1 pellets). Constant outcomes among weeks were also mixed-option (0 or 3 pellets) or single-option (1 pellet). Shifting single-option outcomes among weeks led to better discrimination, more robust preference and significant incentive contrast effects for the alternative outcome. Shifting multioptions altered choice components and led to dissociations among discrimination, preference, and reduced contrast effects. During extinction, all components were impacted with the greatest deficits during the shifting mixed-option outcome sessions. Results suggest choice behavior can be optimized for 1 component but suboptimal for others depending upon the complexity of alterations in outcome value between options. (PsycINFO Database Record
Chapter
Full-text available
The purpose of this review is to present up-to-date pharmacological, genetic, and behavioral findings from the alcohol-preferring P rat and summarize similar past work. Behaviorally, the focus will be on how the P rat meets criteria put forth for a valid animal model of alcoholism with a highlight on its use as an animal model of polysubstance abuse, including alcohol, nicotine, and psychostimulants. Pharmacologically and genetically, the focus will be on the neurotransmitter and neuropeptide systems that have received the most attention: cholinergic, dopaminergic, GABAergic, glutamatergic, serotonergic, noradrenergic, corticotrophin releasing hormone, opioid, and neuropeptide Y. Herein, we sought to place the P rat's behavioral and neurochemical phenotypes, and to some extent its genotype, in the context of the clinical literature. After reviewing the findings thus far, this chapter discusses future directions for expanding the use of this genetic animal model of alcoholism to identify molecular targets for treating drug addiction in general.
Article
Full-text available
The alcohol-preferring, P, rat was developed by selective breeding to study ethanol drinking behavior and its consequences. Characterization of this line indicates the P rat meets all of the criteria put forth for a valid animal model of alcoholism, and displays, relative to their alcohol-non-preferring, NP, counterparts, a number of phenotypic traits associated with alcohol abuse and alcoholism. Behaviorally, compared with NP rats, P rats are less sensitive to the sedative and aversive effects of ethanol and more sensitive to the stimulatory effects of ethanol. Neurochemically, research with the P line indicates the endogenous dopaminergic, serotonergic, GABAergic, opiodergic, and peptidergic systems may be involved in a predisposition for alcohol abuse and alcoholism. Paralleling the clinical literature, genetically selected P rats display levels of ethanol intake during adolescence comparable to that seen during adulthood. Binge drinking has been associated with an increased risk for health and other problems associated with ethanol abuse. A model of binge-like drinking during the dark cycle indicates that P rats will consume 6 g/kg/day of ethanol in as little as three 1-hour access periods/day, which approximates the 24-hour intake of P rats with free-choice access to a single concentration of ethanol. The alcohol deprivation effect (ADE) is a transient increase in ethanol intake above baseline values upon re-exposure to ethanol access after an extended period of deprivation. The ADE has been proposed to be an animal model of relapse behavior, with the adult P rat displaying a robust ADE after prolonged abstinence. Overall, these findings indicate that the P rat can be effectively used in models assessing alcohol-preference, a genetic predisposition for alcohol abuse and/or alcoholism, and excessive drinking using protocols of binge-like or relapse-like drinking.
Article
Full-text available
Drug addiction is often associated with impulsivity and altered behavioural responses to both primary and conditioned rewards. Here we investigated whether selectively bred alcohol-preferring (P) and alcohol-nonpreferring (NP) rats show differential levels of impulsivity and conditioned behavioural responses to food incentives. P and NP rats were assessed for impulsivity in the 5-choice serial reaction time task (5-CSRTT), a widely used translational task in humans and other animals, as well as Pavlovian conditioned approach to measure sign- and goal-tracking behaviour. Drug-naïve P and NP rats showed similar levels of impulsivity on the 5-CSRTT, assessed by the number of premature, anticipatory responses, even when the waiting interval to respond was increased. However, unlike NP rats, P rats were faster to enter the food magazine and spent more time in this area. In addition, P rats showed higher levels of goal-tracking responses than NP rats, as measured by the number of magazine nose-pokes during the presentation of a food conditioned stimulus. By contrast, NP showed higher levels of sign-tracking behaviour than P rats. Following a 4-week exposure to intermittent alcohol we confirmed that P rats had a marked preference for, and consumed more alcohol than, NP rats, but were not more impulsive when re-tested in the 5-CSRTT. These findings indicate that high alcohol preferring and drinking P rats are neither intrinsically impulsive nor do they exhibit impulsivity after exposure to alcohol. However, P rats do show increased goal-directed behaviour to food incentives and this may be associated with their strong preference for alcohol.
Article
Full-text available
Alcoholism afflicts 1 in 13 US adults, and comorbidity with depression is common. Levels of serotonin (5-HT) metabolites in alcoholic or depressed humans and rat strains are lower compared to healthy counterparts. Rats bred for ethanol (EtOH) preference are common in EtOH studies, however out-bred strains better model the range of EtOH consumption in humans. We examined voluntary EtOH consumption in out-bred Sprague-Dawley (SD) rats placed in the 20% EtOH intermittent access drinking paradigm (IA). Acquisition of 20% EtOH consumption (g EtOH/kg/24h) was assessed during the first 6-8 weeks of IA. Rats naturally separated into two groups (Drinkers or Non-drinkers) based on EtOH intake above or below 0.5g/kg/24hr prior to treatment intervention. We examined the effect of central 5-HT depletion on EtOH consumption by infusing 5,7-dihyroxytryptamine (5,7-DHT; i.c.v., 200-300μg) or vehicle and measured EtOH consumption for 4 weeks post-operatively in IA. Compared to baseline, there was no effect of vehicle or 5,7-DHT on EtOH consumption during the post-operative period. Quantification of 5-HT depletion in the dorsal raphe nucleus (DRN) using tryptophan hydroxylase-2 (TPH2) immunohistochemistry resulted in a 76% decrease in staining with 5,7-DHT treatment. Interestingly, preservation of the ventromedial (VM) sub-regions was evident in all animals treated with 5,7-DHT, regardless of drinking behavior. In addition, Drinkers treated with 5,7-DHT had significantly more TPH2 depletion in the DRN compared to Non-drinkers. Our findings indicate that out-bred SD rats exhibit a natural EtOH consumption behavior (Drinker or Non-drinker) that is stable across time and independent of 5-HT depletion in the CNS. In addition, rats that regularly consumed > 0.5g EtOH/kg had greater sensitivity to 5,7-DHT in the DRN, indicating an interaction between EtOH and sensitivity of DRN 5-HT cells to neurotoxic substances. This may contribute to the dysfunctionality of the 5-HT system in alcoholic humans and lead to a better understanding of current pharmacological treatments for this addiction. Copyright © 2015. Published by Elsevier B.V.
Article
Full-text available
Accurate retrospection is critical in many decision scenarios ranging from investment banking to hedonic psychology. A notoriously difficult case is to integrate previously perceived values over the duration of an experience. Failure in retrospective evaluation leads to suboptimal outcome when previous experiences are under consideration for revisit. A biologically plausible mechanism underlying evaluation of temporally extended outcomes is leaky integration of evidence. The leaky integrator favours positive temporal contrasts, in turn leading to undue emphasis on recency. To investigate choice mechanisms underlying suboptimal outcome based on retrospective evaluation, we used computational and behavioural techniques to model choice between perceived extended outcomes with different temporal profiles. Second-price auctions served to establish the perceived values of virtual coins offered sequentially to humans in a rapid monetary gambling task. Results show that lesser-valued options involving successive growth were systematically preferred to better options with declining temporal profiles. The disadvantageous inclination towards persistent growth was mitigated in some individuals in whom a longer time constant of the leaky integrator resulted in fewer violations of dominance. These results demonstrate how focusing on immediate gains is less beneficial than considering longer perspectives.
Chapter
Evolution of Learning and Memory Mechanisms is an exploration of laboratory and field research on the many ways that evolution has influenced learning and memory processes, such as associative learning, social learning, and spatial, working, and episodic memory systems. This volume features research by both outstanding early-career scientists as well as familiar luminaries in the field. Learning and memory in a broad range of animals are explored, including numerous species of invertebrates (insects, worms, sea hares), as well as fish, amphibians, birds, rodents, bears, and human and nonhuman primates. Contributors discuss how the behavioral, cognitive, and neural mechanisms underlying learning and memory have been influenced by evolutionary pressures. They also draw connections between learning and memory and the specific selective factors that shaped their evolution. Evolution of Learning and Memory Mechanisms should be a valuable resource for those working in the areas of experimental and comparative psychology, comparative cognition, brain–behavior evolution, and animal behavior.
Article
Some individuals with alcohol use disorder (AUD) continue to drink because they have developed a habit where they do not consider the consequences of their actions. Genetically selected lines of alcohol preferring and non-preferring rats allow for exploration of how specific endophenotypes, such as tendency to form habits, may be risk factors that interact with a genetic predisposition of AUD. While high alcohol drinking (HAD) and alcohol preferring (P) rats were selectively bred to consume high amounts of freely available ethanol, they exhibit differences in alcohol-seeking behaviors as well as impulsive behaviors and may represent different behavioral models of AUD. The goal of the current study was to compare the tendency to develop habitual behaviors across female and male HAD1, HAD2, and P rats and their respective alcohol non-preferring counterparts. Alcohol-naïve rats were trained on a variable interval schedule using a non-ethanol reinforcer and were then tested in two extinction sessions, one prior to a reinforcer devaluation (conditioned taste aversion) procedure and one after. There were no differences in total lever presses between P and alcohol non-preferring (NP) rats, but there were differences between HAD and low-alcohol drinking (LAD) rats. All six strains decreased lever pressing after reinforcer devaluation. However, P and NP females did not increase latency to first lever press after devaluation, suggesting some inclination towards habitual behavior that was not apparent in either the HAD/LAD lines. Selective breeding for alcohol preference does not seem to influence the tendency to form habits, whereas background strain and sex may have an influence on this behavior.
Article
Alcohol use disorder (AUD) constitutes a major burden to global health. Recently, the translational success of animal models of AUD has come under increased scrutiny. Efforts to refine models to gain a more precise understanding of the neurobiology of addiction are warranted. Appetitive responding for ethanol (seeking) and its consumption (taking) are governed by distinct neurobiological mechanisms. However, consumption is often inferred from appetitive responding in operant ethanol self-administration paradigms, preventing identification of distinct experimental effects on seeking and taking. In the present study, male Long-Evans, Wistar, and Sprague-Dawley rats were trained to lever press for ethanol using a lickometer-equipped system that precisely measures both appetitive and consummatory behavior. Three distinct operant phenotypes emerged during training: 1) Drinkers, who lever press and consume ethanol; 2) Responders, who lever press but consume little to no ethanol; and 3) Non-responders, who do not lever press. While the prevalence of each phenotype differed across strains, appetitive and consummatory behavior was similar across strains within each phenotype. Appetitive and consummatory behaviors were significantly correlated in Drinkers, but not Responders. Analysis of drinking microstructure showed that greater consumption in Drinkers relative to Responders is due to increased incentive for ethanol rather than increased palatability. Importantly, withdrawal from chronic ethanol exposure resulted in a significant increase in appetitive responding in both Drinkers and Responders, but only Drinkers exhibited a concomitant increase in ethanol consumption. Together, these data reveal important strain differences in appetitive and consummatory responding for ethanol and uncover the presence of distinct operant phenotypes.
Article
Sugar has been shown to be a powerful substitute for drugs in preclinical studies on addiction. However, the link between sugar intake and alcohol use disorder (AUD) is poorly understood. We assessed the influence of sucrose on ethanol drinking in both nondependent (ND) and dependent (D) Long-Evans rats during acute withdrawal using the postdependent state model. Ethanol (10%-40%) and sucrose (1%-4%) solutions were offered in an operant paradigm either independently or concurrently under ratio schedules of reinforcement. We showed that D rats displayed an enhanced motivation for both 10% ethanol solution (10E) and 4% sucrose solution (4S) as compared with ND rats, and a clear preference for 4S was observed in both groups. During acute withdrawal, D rats showed a strong motivation for 30% ethanol (30E), even when adulterated with quinine, but still preferred 4S despite the fact that a high level of negative reinforcement could be expected. However, when a premix solution (30E4S) was offered concurrently with 4S, the preference for 4S was lost in D animals, which consumed as much premix as 4S, whereas ND animals displayed preference for 4S. Altogether, those results suggest that reinforcing properties of sucrose surpass those of ethanol in D rats under acute withdrawal, which indicates that sugar is a powerful substitute for ethanol. Our results suggest that craving for sugar may be increased in AUD patients during withdrawal and raise the issue of dependence transfer from alcohol to sugar.
Article
Alcohol use disorder (AUD) is characterized by impairments in decision‐making that can exist as stable traits or transient states. Cognitive inflexibility reflects an inability to update information that guides decision‐making and is thought to contribute to the inability to abstain from drinking. While several studies have reported evidence of impaired cognitive flexibility following chronic alcohol exposure, evidence that a pre‐existing impairment in cognitive flexibility is a heritable risk factor for AUD is scarce. Here, we found that cognitive flexibility was impaired in rodents selectively bred for excessive alcohol consumption (alcohol preferring (P) rats), on the attentional set‐shifting task (ASST). Further, the degree of impairment is predictive of future ethanol consumption, thus suggesting that cognitive inflexibility is a stable trait capable of predisposing one for drinking. In a second set of experiments, we observed an impairment in the ability of P rats to use a previously learned rule to guide foraging in a simple discrimination task. Convergence across several behavioral measures suggested that this impairment reflected a state of heightened urgency that interfered with decision‐making. A similar impairment on a simple discrimination task was observed in Wistar rats with a history of alcohol consumption. These findings indicate how trait and state variables—in this case, impaired cognitive flexibility and heightened urgency, respectively—may influence the risk for excessive drinking. Furthermore, our results suggest that cognitive inflexibility and urgency can exist as both risk factors for and the result of alcohol exposure.
Article
Increased subjective discounting of delayed rewards is associated with substance abuse, and individuals tend to discount their drug of choice at a greater rate compared to monetary rewards. While there is evidence indicating that increased delay discounting (DD) is a risk factor for substance abuse, some results suggest that exposure to drugs of abuse also increases DD, but effects are mixed. The current study examined whether ethanol pre-exposure increases DD and if an ethanol reinforcer would be discounted at a greater rate than sucrose. Alcohol preferring (P) rats were pre-exposed to either ethanol or sucrose using an intermittent access protocol (IAP) for 8 weeks. Then animals completed an operant fixed choice procedure where each pre-exposure group was split into either an ethanol or sucrose reinforcer group. Afterwards, animals completed an adjusting delay DD task using the same groups as the fixed choice task. Animals that received access to ethanol in the IAP showed increased delayed reward preference in a delay and session dependent manner. Specifically, ethanol pre-exposed animals took more sessions to decrease their preference for the delayed reward at longer delays. In the adjusting delay task, no differences in mean adjusting delays were seen, but ethanol pre-exposure impaired animals' ability to reach stability criteria. The observed results are not consistent with ethanol pre-exposure causing a change in DD. Rather they indicate ethanol pre-exposure impaired animals' ability to reallocate their behavior in response to a change in reinforcer contingencies. The current findings extend prior results showing alcohol naïve P rats exhibit both increased DD and decreased response inhibition (Beckwith and Czachowski 2014, 2016) by demonstrating that after alcohol exposure they exhibit a form of behavioral inflexibility. Hence, a "two-hit" genetic vulnerability/environmental acceleration of addictive behavior is supported.
Article
Adolescent alcohol drinking has been linked to increased risk for drug abuse during adulthood. Nicotine microinjected directly into the posterior ventral tegmental area (pVTA) stimulates dopamine (DA) release in the nucleus accumbens (NAc) shell. The α7 nicotinic acetylcholine receptor (nAChR) is a potent regulator of dopaminergic activity in the pVTA. The current experiments examined the effects of peri-adolescent ethanol (EtOH) drinking on the ability of intra-pVTA nicotine to stimulate DA release during adulthood and alterations in α7 nAChR expression within the pVTA. Alcohol-preferring (P) female rats consumed EtOH and/or water during adolescence (post-natal day [PND] 30-60) or adulthood (PND 90-120). Thirty days following removal of EtOH, subjects received microinjections of 1 μM, 10 μM, or 50 μM nicotine into the pVTA concurrently with microdialysis for extracellular DA in the NAc shell. Brains were harvested from an additional cohort after PND 90 for quantification of α7 nAChR within the pVTA. The results indicated that only adolescent EtOH consumption produced a leftward and upward shift in the dose response curve for nicotine to stimulate DA release in the NAc shell. Investigation of α7 nAChR expression within the pVTA revealed a significant increase in animals that consumed EtOH during adolescence compared to naïve animals. The data suggests that peri-adolescent EtOH consumption produced cross-sensitization to the effects of nicotine during adulthood. The interaction between adolescent EtOH consumption and inflated adult risk for drug dependency could be predicated, at least in part, upon alterations in α7 nAChR expression within the mesolimbic reward pathway.
Article
Overconsumption of sugars contributes to poor health outcomes. Sugars are often added to commercial foods and beverages in low concentrations and these hidden sugars are consumed unnoticed, continuously. These hidden sugars are suggested to increase the motivation for foodstuffs with higher sugar contents, due to their rewarding properties. This process has been attributed in part, to the activity of both dopaminergic and opioidergic systems in the nucleus accumbens. We asked the question whether prolonged continuous consumption of a low concentration sucrose solution was sufficient to trigger alterations in both dopaminergic and opioidergic systems in the nucleus accumbens of male Sprague-Dawley rats. Rats were given access to either, 1% sucrose and water ad libitum for 3 weeks, or water alone, we then assayed the nucleus accumbens for mRNA and protein expression levels of D1 and D2 dopamine receptors which mediate appetitive motivation and wanting behaviors and for μ-opioid receptors which mediate liking of rewarding stimuli. Our data revealed that rats express a strong preference for 1% sucrose, and showed increased μ-opioid receptor mRNA expression bilaterally in the nucleus accumbens; increased D1 receptor mRNA expression in the left nucleus accumbens; and increased D2 receptor mRNA expression and decreased D2 receptor protein expression in the right nucleus accumbens. We also noted clear individual differences in the volumes of sucrose ingested over this period, however these differences did not correlate with the changes in neurochemistry. Our data show that prolonged ad libitum access to low concentration sucrose alters brain circuits critical for coding reward which may contribute to an enhanced drive for sweet foods and beverages.
Article
Social interactions/situations have dramatic influences on motivation. Creating animal models examining these influences promotes a better understanding of the psychological and biological underpinnings of social motivation. Rodents are sensitive to social history/experience during associative conditioning and food-sharing tasks. Would reward-oriented operant behavior be sensitive to social influences by showing a negative contrast-like effect when another organism obtains a greater value outcome? We used a side-by-side arrangement of operant response chambers wherein one animal obtained consistently high reward signaled by a discrete cue. The neighboring, experimental rat experienced different combinations of high and low reward trial sequences. Control conditions included distraction from a conspecific in the neighboring chamber (rat distractor) or cue/food dispenser operating without a conspecific (program distractor) in addition to testing subjects alone. Results support an influence of the other animal actively performing the task on the experimental subject’s behavior. Primarily, responding was significantly slower for the low reward trials while the neighboring rat was receiving the higher magnitude reward. The lever-press and not food-cup retrieval latency was significantly slower during exposure to a conspecific neighbor performing the operant task. The effect was not obtained in all session sequences and was more pronounced using longer series of consecutive low reward trials. The slowing effect was also obtained with the program-distractor experience in a different trial sequence. These findings suggest a social-induced negative incentive contrast effect in rats possibly mediated by an outcome inequity process that could have key similarities to complex situational-affective effects on motivation involving frustration or jealously.
Article
Alcohol consumption impairs judgment and choice. How alcohol alters these crucial processes is primarily unknown. Choice can be fractionated into different components including reward discrimination, preference and relative valuation that can function together or in isolation depending upon diverse factors including choice context. We examined the diverse components and contextual effects by analyzing the effects of alcohol drinking on choice behavior in a task with a reduced level of temporal and spatial constraints. Rats were trained to drink 10% ethanol during 6 weeks of behavior testing using a combined sucrose-fade and two-bottle free-choice procedure. Two different sucrose pellet outcomes (e.g., constant vs. variable) were presented each week to examine the impact of voluntary drinking on reward-based decision-making. Behavioral contexts of single option, free choice and extinction were examined for each outcome set. Comparisons were made between alcohol and control groups and within the alcohol group over time to inspect choice profiles. Between-group results showed alcohol drinking animals expressed altered place preference, and modified sucrose reward approach latencies. The within-group profile showed that alcohol drinking animals can express adequate reward discrimination, preference, and incentive contrast during free choice. All of these components were significantly reduced during the context of extinction. Control animals were also impacted by extinction but not as severely. The findings point to a need for a greater focus on the context and the diverse components of choice when examining external and internal factors influencing decision-making during alcohol or other substance of abuse exposure. This article is protected by copyright. All rights reserved.
Article
Previous research has implicated the positive modulation of anandamide, an endocannabinoid neurotransmitter, on feeding behavior. Anandamide is particularly noteworthy as it acts as an endogenous ligand of the CB1 receptor, the same receptor that is activated by tetrahydrocannabinol, the primary psychoactive component in Cannabis sativa. Cannabis legalization in North America has presented with a need to study endocannabinoid agonists and their effects on behavior. Much has yet to be determined in terms of the role of the endocannabinoid system in decision-making scenarios. The research presented here tested the hypothesis that anandamide would augment motivation and reward processing via appetitive and consummatory measures during an operant, foraging task. A three-box design was used in order to provide the animals with a free choice, exploratory foraging environment. Discrimination, preference, and incentive contrast were analyzed as discrete measures of decision-making in the three-box paradigm. Anandamide administration (1mg/kg) was found to significantly increase motivation for the optimal foraging outcome and alter basic processing of reward information involved in discrimination and relative valuation. The positive effects of anandamide on eating behavior and motivation have implications toward possible treatment modalities for patient populations presenting with disorders of motivation. These findings suggest the need for continued investigation of the endocannabinoid system as a central component of motivated behavior.
Article
The striatum is a key structure involved in reward processing and choice. Recently, we have developed a paradigm to explore how components of reward processing work together or independently during choice behavior. These components include reward discrimination, preference and relative valuation, and the goal of the present study was to determine how the striatum is involved in these dissociable components during this novel free choice paradigm. We tested choice utilizing two different outcome series with one being a more straightforward single-option discrimination anchored by a 0 reward outcome, and the other as a multi-option outcome discrimination of greater difficulty. We compared the free choice reward task to a sequential reward task and an extinction task. Striatal lesions impaired responding only in the free choice version with alterations in both appetitive and consummatory measures. Ventral striatal lesions had greater impact altering discrimination, preference and relative valuation in both the single and multi-option week studies. A major factor involved in these deficits was a significant aversion to the multi-option that contained a larger outcome option but with a longer delay to reward. Dorsal striatal lesions caused less impairment even leading to enhanced choice behavior compared to control animals during the more difficult multi-option free choice series. Overall, the results suggest that the context of action is crucial when linking striatal function to choice behavior and its diverse components. The implications include the idea that striatal involvement in decision-making is increased when responses are self-paced and diverse in a more naturalistic environment.
Article
Exposing rats to an upshift from a small reward to a larger reward sometimes yields evidence of consummatory successive positive contrast (cSPC), an effect that could be a suitable animal model of positive emotion. However, cSPC is an unreliable effect. Ten experiments explored the effects of an upshift in sucrose or saccharin concentration on consummatory behavior under several conditions. There was occasional evidence of cSPC, but mostly a combination of increased consummatory behavior relative to preshift reward concentrations and a reduced behavioral level relative to unshifted controls. Such a pattern is consistent with processes causing opposite changes on behavior. Reward upshift may induce processes that suppress behavior, such as taste neophobia (induced by an intense sucrose taste) and generalization decrement (induced by novelty in reward conditions after the upshift). An experiment tested the role of such novelty-related effects by preexposing animals to either the upshift concentration (12% sucrose) or water during three days before the start of the experiment. Sucrose-preexposed animals drank significantly more than water-preexposed animals during the upshift, but just as much as unshifted controls (i.e., no evidence of cSPC). These results suggest that cSPC may be difficult to obtain reliably because reward upshift induces opposing processes. However, they also seriously question the ontological status of cSPC.
Article
Food restriction is a defining characteristic of anorexia nervosa and a risk factor for binge pathology. Basic research related to drug addiction indicates that food restriction increases drug reward magnitude, persistence of preference for a drug-paired environment, and relapse to drug seeking. These phenomena suggest that drugs of abuse subvert the adaptive mechanisms that normally facilitate foraging, learning, and ingestion when food is scarce. Similarly, if supranormally rewarding, energy-dense food is abundant but the physiological effects of underfeeding prevail due to restricted intake, the risk of developing maladaptive addiction-like eating behavior may increase. In this chapter, methods are described for assessing neurotransmitter receptor mechanisms and intracellular signaling pathways in the nucleus accumbens (NAc) that contribute to enhanced reward sensitivity in food-restricted rats. These methods combine intracerebral drug microinjection with the curve-shift rate-frequency protocol of intracranial self-stimulation testing. The addition of continuous intraventricular infusion of metabolic hormone or feeding-related neuropeptide receptor ligands is described as a means of assessing peripheral responses that may be antecedents to central nervous system changes of interest. When these studies are guided by biochemical findings in the NAc of food-restricted rats, the approach enables identification of neuroadaptations that increase reward sensitivity and suggests others that may increase synaptic plasticity and ingrain behavior. The goal is to generate a set of defined candidate mechanisms that can be evaluated for their involvement in the development and maintenance of disordered eating.
Article
The question of addiction concerns the process by which drug-taking behavior, in certain individuals, evolves into compulsive patterns of drug-seeking and drug-taking behavior that take place at the expense of most other activities, and the inability to cease drug-taking, that is, the problem of relapse. In this paper we summarize one view of this process, the “incentive-sensitization” view, which we e rst proposed in 1993. Four major tenets of the incentive-sensitization view are discussed. These are: (1) potentially addictive drugs share the ability to alter brain organization; (2) the brain systems that are altered include those normally involved in the process of incentive motivation and reward; (3) the critical neuroadaptations for addiction render these brain reward systems hypersensitive (“sensitized”) to drugs and drug-associated stimuli; and (4) the brain systems that are sensitized do not mediate the pleasurable or euphoric effects of drugs (drug “liking”), but instead they mediate a subcomponent of reward we have termed incentive salience (drug “wanting”).
Article
Two groups of male albino rats were given one trial a day in a Lashley maze under high deprivation conditions and received either 1 or 22 pellets (Phase 1). This particular maze was used as a control for slowing the Ss’ running speed. Following stable performance in Phase 1, each group was subdivided into a high and low drive condition, and each S received 22 pellets (Phase 2). In Phase 3, all Ss were extinguished under the same drive conditions prevailing in Phase 2. It was found that the large-reward Ss ran significantly faster than the small-reward Ss in Phase 1. Regardless of drive conditions, the Ss that had received small reward in Phase 1 ran significantly faster in both Phases 2 and 3 than those that had received large reward. The results were interpreted in terms of absolute and relative views of reinforcement.
Article
Comparing different rewards automatically produces dynamic relative outcome effects on behavior. Each new outcome exposure is to an updated version evaluated relative to alternatives. Relative reward effects include incentive contrast, positive induction and variety effects. The present study utilized a novel behavioral design to examine relative reward effects on a chain of operant behavior using auditory cues. Incentive contrast is the most often examined effect and focuses on increases or decreases in behavioral performance after value upshifts (positive) or downshifts (negative) relative to another outcome. We examined the impact of comparing two reward outcomes in a repeated measures design with three sessions: a single outcome and a mixed outcome and a final single outcome session. Relative reward effects should be apparent when comparing trials for the identical outcome between the single and mixed session types. An auditory cue triggered a series of operant responses (nosepoke-leverpress-food retrieval), and we measured possible contrast effects for different reward magnitude combinations. We found positive contrast for trials with the greatest magnitude differential but positive induction or variety effects in other combinations. This behavioral task could be useful for analyzing environmental or neurobiological factors involved in reward comparisons, decision-making and choice during instrumental, goal-directed action.
Article
Weight-loss dieting often leads to loss of control, rebound weight gain, and is a risk factor for binge pathology. Based on findings that food restriction (FR) upregulates sucrose-induced trafficking of glutamatergic AMPA receptors to the nucleus accumbens (NAc) postsynaptic density (PSD), this study was an initial test of the hypothesis that episodic "breakthrough" intake of forbidden food during dieting interacts with upregulated mechanisms of synaptic plasticity to increase reward-driven feeding. Ad libitum (AL) fed and FR subjects consumed a limited amount of 10% sucrose, or had access to water, every other day for ten occasions. Beginning three weeks after return of FR rats to AL feeding, when 24-hour chow intake and rate of body weight gain had normalized, subjects with a history of sucrose intake during FR consumed more sucrose during a four week intermittent access protocol than the two AL groups and the group that had access to water during FR. In an experiment that substituted noncontingent administration of d-amphetamine for sucrose, FR subjects displayed an enhanced locomotor response during active FR but a blunted response, relative to AL subjects, during recovery from FR. This result suggests that the enduring increase in sucrose consumption is unlikely to be explained by residual enhancing effects of FR on dopamine signaling. In a biochemical experiment which paralleled the sucrose behavioral experiment, rats with a history of sucrose intake during FR displayed increased abundance of pSer845-GluA1, GluA2, and GluA3 in the NAc PSD relative to rats with a history of FR without sucrose access and rats that had been AL throughout, whether they had a history of episodic sucrose intake or not. A history of FR, with or without a history of sucrose intake, was associated with increased abundance of GluA1. A terminal 15-min bout of sucrose intake produced a further increase in pSer845-GluA1 and GluA2 in subjects with a history of sucrose intake during FR. Generally, neither a history of sucrose intake nor a terminal bout of sucrose intake affected AMPA receptor abundance in the NAc PSD of AL subjects. Together, these results are consistent with the hypothesis, but the functional contribution of increased synaptic incorporation of AMPA receptors remains to be established. Copyright © 2015. Published by Elsevier Ltd.
Article
Background Delay discounting (DD) is a measure of impulsivity that quantifies preference for a small reward delivered immediately over a large reward delivered after a delay. It has been hypothesized that impulsivity is an endophenotype associated with increased risk for development of alcohol use disorders (AUDs); however, a causal role of impulsivity is difficult to determine with human studies. We tested this hypothesis by assessing the degree of DD present in alcohol-naïve rats selectively bred for either high- or low-alcohol preference.MethodsA novel adaptation of a within-sessions DD procedure was used to compare impulsivity differences between male alcohol-preferring (P) and nonpreferring (NP) rat lines (n = 6 per line) using a 5% sucrose reward. Animals chose between 2 options: 2-second sipper tube access delivered immediately (small reward) or 8-second access after a variable delay (large reward). Each 50-minute session consisted of 5 blocks of ten 60-second trials. Within each session, the delay to the large reward increased in each block of trials. Delays were gradually increased over 3 sets to attain a final delay set of 3, 8, 15, 18, and 25 seconds.ResultsPrior to starting delays, there were no significant differences between lines in sucrose consumption or percent choice for the large reward, and both lines exhibited a clear preference for the large reward. After delays were initiated, choice for the large reward decreased as the delay to its presentation increased. Although discounting of the large, delayed reward was observed for both lines, the degree of discounting, or “impulsivity,” was greater for P rats compared with NP rats.ConclusionsP rats are more impulsive for sucrose rewards before exposure to alcohol compared with NP rats. Thus, individuals genetically predisposed toward developing AUDs may be more likely to engage in impulsive decision making prior to alcohol exposure.
Article
Sucrose reinforcement thresholds were determined for bar pressing. Hungry Ss showed lower thresholds than non-deprived Ss and thirsty Ss did not prefer sucrose at all.
Article
Rats maintained at either 75% or 90% of their ad lib weight were trained to run in a straight alley for either a 10- or 1-pellet reward. Following 15 days (30 trials) of acquisition training, the 10-pellet groups were shifted to 1 pellet. A significant negative contrast was obtained only with the 75% rats and only in the goal region of the alley. The effects of deprivation on contrast found in this study were consistent with those found in earlier studies and consistent with the effects of deprivation on a number of other extinction-related phenomena.