Everitt BJ, Robbins TW. Neural systems of reinforcement for drug addiction: from actions to habits to compulsion. Nat Rev Neurosci 8: 1481-1489

Department of Experimental Psychology and the MRC-Wellcome Behavioural and Clinical Neuroscience Institute, University of Cambridge, Downing Street, Cambridge CB2 3EB, UK.
Nature Neuroscience (Impact Factor: 16.1). 12/2005; 8(11):1481-9. DOI: 10.1038/nn1579
Source: PubMed


Drug addiction is increasingly viewed as the endpoint of a series of transitions from initial drug use--when a drug is voluntarily taken because it has reinforcing, often hedonic, effects--through loss of control over this behavior, such that it becomes habitual and ultimately compulsive. Here we discuss evidence that these transitions depend on interactions between pavlovian and instrumental learning processes. We hypothesize that the change from voluntary drug use to more habitual and compulsive drug use represents a transition at the neural level from prefrontal cortical to striatal control over drug seeking and drug taking behavior as well as a progression from ventral to more dorsal domains of the striatum, involving its dopaminergic innervation. These neural transitions may themselves depend on the neuroplasticity in both cortical and striatal structures that is induced by chronic self-administration of drugs.

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Available from: Barry John Everitt, Apr 10, 2014
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    • "One could speculate that the approach bias may only be evident in early stages of cannabis abuse, predicting escalation of cannabis use rather than problem severity. This is in line with addiction models that suggest that motivational processes, like attentional and approach bias may play a role when substance use is still under voluntary control (Di Chiara, 2000; Everitt and Robbins, 2005). Yet, craving, but not cognitive control, predicted treatment progress, contradicting these same models. "
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    ABSTRACT: Cannabis use disorders (CUDs) are the most prevalent substance use disorders among adolescents in treatment. Yet, little is known about the neuropsychological mechanisms underlying adolescent CUDs. Studies in adult cannabis users suggest a significant role for cognitive control and cannabis-oriented motivational processes, such as attentional bias, approach bias, and craving in CUDs. The current 6-month prospective study investigated the relationships between attentional bias, approach bias, craving, cognitive control, and cannabis use in adolescent patients in treatment for a primary or secondary CUD. Moreover, we investigated if these motivational processes and cognitive control could predict treatment progression after 6 months. Adolescents with a CUD had an attentional but no approach bias towards cannabis. In contrast to adult findings on the role of attentional bias, approach bias and cognitive control, only cannabis craving significantly correlated with current cannabis use and predicted cannabis use-related problems and abstinence from cannabis 6 months later. These findings identify craving as a predictor of treatment outcome, thereby supporting an important role for craving in the course of adolescent cannabis use and dependence. This prospective study is among the first to investigate neuropsychological mechanisms underlying adolescent CUDs, warranting future longitudinal studies. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
    Full-text · Article · Apr 2015 · Developmental Cognitive Neuroscience
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    • "These findings may reflect impaired communication across parallel corticostriatal circuits in the dopamine-deprived striatum in Parkinson's disease. A recent body of neuroanatomical data has revealed the existence of striato-nigro-striatal circuitry, comprised of spiraling neuronal connections between the striatum and the dopaminergic midbrain (substantia nigra/ ventral tegmental area) (Haber, 2003; Haber et al., 2000), which have been shown to enable transfer of information across functional subdivisions of the striatum (Belin and Everitt, 2008; Everitt and Robbins, 2005; Porrino et al., 2007; Volkow et al., 2006). Although fMRI is unable to disentangle the underlying cellular mechanisms by which dopaminergic pathology compromises connectivity across striatal subdivisions in Parkinson's disease, impaired dopaminergic neurotransmission throughout striato-nigro-striatal circuitry represents an important candidate mechanism. "
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    ABSTRACT: The pathological hallmark of Parkinson’s disease is the degeneration of dopaminergic nigrostriatal neurons, leading to depletion of striatal dopamine. Recent neuroanatomical work has identified pathways for communication across striatal subdivisions, suggesting that the striatum provides a platform for integration of information across parallel corticostriatal circuits. The aim of this study was to investigate whether dopaminergic dysfunction in Parkinson’s disease was associated with impairments in functional connectivity across striatal subdivisions, which could potentially reflect reduced integration across corticostriatal circuits. Utilizing resting-state functional magnetic resonance imaging (fMRI), we analyzed functional connectivity in 39 patients with Parkinson’s disease, both “on” and “off” their regular dopaminergic medications, along with 40 age-matched healthy controls. Our results demonstrate widespread impairments in connectivity across subdivisions of the striatum in patients with Parkinson’s disease in the “off” state. The administration of dopaminergic medication significantly improved connectivity across striatal subdivisions in Parkinson’s disease, implicating dopaminergic deficits in the pathogenesis of impaired striatal interconnectivity. In addition, impaired striatal interconnectivity in the Parkinson’s disease “off” state was associated with pathological decoupling of the striatum from the thalamic and sensorimotor (SM) networks. Specifically, we found that although the strength of striatal interconnectivity was positively correlated with both (i) the strength of internal thalamic connectivity, and (ii) the strength of internal SM connectivity, in both healthy controls and the Parkinson’s disease “on” state, these relationships were absent in Parkinson’s disease when in the “off” state. Taken together our findings emphasize the central role of dopamine in integrated striatal function and the pathological consequences of striatal dopamine denervation in Parkinson’s disease.
    Full-text · Article · Apr 2015 · Human Brain Mapping
    • "These studies point to the nucleus accumbens (NAcc) as an important mediating brain structure (Bray et al. 2008; Talmi et al. 2008; Prevost et al. 2012; Geurts et al. 2013; Lewis et al. 2013; Mendelsohn et al. 2014), hypothetically via cue-induced dopamine release (Robbins & Everitt 1999; Kienast & Heinz 2006). Findings in human subjects line up with lesion studies in animals where the NAcc has also been identified as a crucial neural substrate for PIT (Corbit, Muir & Balleine 2001; Everitt, Dickinson & Robbins 2001; Corbit & Balleine 2005; Corbit & Janak 2007b; Saddoris et al. 2011; Pecina & Berridge 2013; Ostlund et al. 2014). The NAcc as part of the ventral striatum is a core area of the so-called reward system (Volkow et al. 1996, 2009; Breiter et al. 2001) and has been implicated in mechanisms promoting cue reactivity, e.g. "
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    ABSTRACT: In detoxified alcohol-dependent patients, alcohol-related stimuli can promote relapse. However, to date, the mechanisms by which contextual stimuli promote relapse have not been elucidated in detail. One hypothesis is that such contextual stimuli directly stimulate the motivation to drink via associated brain regions like the ventral striatum and thus promote alcohol seeking, intake and relapse. Pavlovian-to-Instrumental-Transfer (PIT) may be one of those behavioral phenomena contributing to relapse, capturing how Pavlovian conditioned (contextual) cues determine instrumental behavior (e.g. alcohol seeking and intake). We used a PIT paradigm during functional magnetic resonance imaging to examine the effects of classically conditioned Pavlovian stimuli on instrumental choices in n = 31 detoxified patients diagnosed with alcohol dependence and n = 24 healthy controls matched for age and gender. Patients were followed up over a period of 3 months. We observed that (1) there was a significant behavioral PIT effect for all participants, which was significantly more pronounced in alcohol-dependent patients; (2) PIT was significantly associated with blood oxygen level-dependent (BOLD) signals in the nucleus accumbens (NAcc) in subsequent relapsers only; and (3) PIT-related NAcc activation was associated with, and predictive of, critical outcomes (amount of alcohol intake and relapse during a 3 months follow-up period) in alcohol-dependent patients. These observations show for the first time that PIT-related BOLD signals, as a measure of the influence of Pavlovian cues on instrumental behavior, predict alcohol intake and relapse in alcohol dependence. © 2015 Society for the Study of Addiction.
    No preview · Article · Apr 2015 · Addiction Biology
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