Neural systems of reinforcement for drug addiction: from actions to habits to compulsion

Everitt, Barry J.; Robbins, Trevor W.

doi:10.1038/nn1579

Cited by 3,366 publications

(3,150 citation statements)

References 99 publications

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“…Along the same lines, amphetamine pre-treatment speeds up the rate at which the outcome insensitivity develops (Nelson and Killcross, 2006), and this depends particularly on D 1 rather than D 2 receptors (Nelson and Killcross, 2013). In humans, there is evidence for enhanced habitization in obsessive-compulsive disorder (Everitt and Robbins, 2005;Robbins et al, 2012;Gillan et al, 2011Gillan et al, , 2013 and forthcoming evidence in cocaine addiction (N. Daw and V. Voon, personal communication), but not yet in alcohol addiction (Sebold et al, subm).…”

Section: Individual Variability In Addiction Vulnerabilitymentioning

confidence: 96%

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The role of learning-related dopamine signals in addiction vulnerability

Huys

Tobler

Hasler

et al. 2014

Progress in Brain Research

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Psychostimulants such as methylphenidate (MPH) and antidepressants such as fluoxetine (FLX) are widely used in the treatment of various mental disorders or as cognitive enhancers. These medications are often combined, for example, to treat comorbid disorders. There is a considerable body of evidence from animal models indicating that individually these psychotropic medications can have detrimental effects on the brain and behavior, especially when given during sensitive periods of brain development. However, almost no studies investigate possible interactions between these drugs. This is surprising given that their combined neurochemical effects (enhanced dopamine and serotonin neurotransmission) mimic some effects of illicit drugs such as cocaine and amphetamine. Here, we summarize recent studies in juvenile rats on the molecular effects in the mid-and forebrain and associated behavioral changes, after such combination treatments. Our findings indicate that these combined MPH + FLX treatments can produce similar molecular changes as seen after cocaine exposure while inducing behavioral changes indicative of dysregulated mood and motivation, effects that often endure into adulthood. Tables: 2 References: 254 ABSTRACT Dopaminergic signals play a mathematically precise role in reward-related learning, and variations in dopaminergic signalling have been implicated in vulnerability to addiction. Here, we provide a detailed overview of the relationship between theoretical, mathematical and experimental accounts of phasic dopamine signalling, with implications for the role of learning-related dopamine signalling in addiction and related disorders. We describe the theoretical and behavioural characteristics of model-free learning based on errors in the prediction of reward, including step-by-step explanations of the underlying equations. We then use recent insights from an animal model that highlights individual variation in learning during a Pavlovian conditioning paradigm to describe overlapping aspects of incentive salience attribution and model-free learning. We argue that this provides a computationally coherent account of some features of addiction. CONTENTS

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Section: Individual Variability In Addiction Vulnerabilitymentioning

confidence: 96%

“…This forms the core of the actor-critic model (Barto et al, 1983;O'Doherty et al, 2004). Experimentally, it is perhaps most directly demonstrated by conditioned reinforcement experiments (Everitt and Robbins, 2005;Meyer et al, 2012), where instrumental behaviours can be reinforced by Pavlovian CSs.…”

Section: Instrumental Behaviourmentioning

confidence: 98%

The role of learning-related dopamine signals in addiction vulnerability

Huys

Tobler

Hasler

et al. 2014

Progress in Brain Research

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“…Relevant to addiction, Homer transcripts or proteins are present in many of the structures within mesocorticolimbic circuits that exhibit pathology in addiction [cf. 2,4,23,53,[151][152][153][154][155][156]. CC-Homer and IEG Homer isoforms are found throughout the cerebral cortex [105,106].…”

Section: Homers Are Regulated Within Addiction-related Neural Circuitmentioning

confidence: 99%

Homers regulate drug-induced neuroplasticity: Implications for addiction

Szumlinski

Ary

Lominac

2008

Biochemical Pharmacology

118

160

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Drug addiction is a chronic, relapsing disorder, characterized by an uncontrollable motivation to seek and use drugs. Converging clinical and preclinical observations implicate pathologies within the corticolimbic glutamate system in the genetic predisposition to, and the development of, an addicted phenotype. Such observations pose cellular factors regulating glutamate transmission as likely molecular candidates in the etiology of addiction. Members of the Homer family of proteins regulate signal transduction through, and the trafficking of, glutamate receptors, as well as maintain and regulate extracellular glutamate levels in corticolimbic brain regions. This review summarizes the existing data implicating the Homer family of protein in acute behavioral and neurochemical sensitivity to drugs of abuse, the development of drug-induced neuroplasticity, as well as other behavioral and cognitive pathologies associated with an addicted state.

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“…Numerous explanations for addiction to opioid and DA receptor stimulation have been offered. Examples include intracellular changes involving gene expression in the NAc [62], habit learning [63], loss of cortical executive control [64], abstinence-induced incubation of the reinstatement of responding for drug-related cues [65], and a cycle of unpleasant withdrawal effects, including conditioned withdrawal, that leads to self-medication with the drug in an effort to regain normalcy [66]. These processes are not mutually exclusive, and several may involve DA in one site or another.…”

Section: Drug Self-administration and Drug Withdrawalmentioning

confidence: 99%

Accumbens dopamine-acetylcholine balance in approach and avoidance

Hoebel

Avena

Rada

2007

Current Opinion in Pharmacology

154

117

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SummaryUnderstanding systems for approach and avoidance is basic for behavioral neuroscience. Research on the neural organization and functions of the dorsal striatum in movement disorders, such as Huntington's and Parkinson's Disease, can inform the study of the nucleus accumbens (NAc) in motivational disorders, such as addiction and depression. We propose opposing roles for dopamine (DA) and acetylcholine (ACh) in the NAc in the control of GABA output systems for approach and avoidance. Contrary to DA, which fosters approach, ACh release is a correlate or cause of meal satiation, conditioned taste aversion and aversive brain stimulation. ACh may also counteract excessive DA-mediated approach behavior as revealed during withdrawal from drugs of abuse or sugar, when the animal enters an ACh-mediated state of anxiety and behavioral depression. This review summarizes evidence that ACh is important in the inhibition of behavior when extracellular DA is high and the generation of an anxious or depressed state when DA is relatively low.

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Neural systems of reinforcement for drug addiction: from actions to habits to compulsion

Cited by 3,366 publications

References 99 publications

The role of learning-related dopamine signals in addiction vulnerability

The role of learning-related dopamine signals in addiction vulnerability

Homers regulate drug-induced neuroplasticity: Implications for addiction

Accumbens dopamine-acetylcholine balance in approach and avoidance

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