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

doi:10.1038/NN1579

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

Journal Article•DOI•

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

Barry J. Everitt¹, Trevor W. Robbins¹•Institutions (1)

University of Cambridge¹

01 Nov 2005-Nature Neuroscience (Nature Publishing Group)-Vol. 8, Iss: 11, pp 1481-1489

TL;DR: It is hypothesized 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.

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Abstract: 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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Journal Article•DOI•

Neurocircuitry of Addiction

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George F. Koob¹, Nora D. Volkow²•Institutions (2)

Scripps Research Institute¹, National Institute on Drug Abuse²

01 Jan 2010-Neuropsychopharmacology

TL;DR: The delineation of the neurocircuitry of the evolving stages of the addiction syndrome forms a heuristic basis for the search for the molecular, genetic, and neuropharmacological neuroadaptations that are key to vulnerability for developing and maintaining addiction.

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4,160 citations

Journal Article•DOI•

The reward circuit: linking primate anatomy and human imaging.

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Suzanne N. Haber¹, Brian Knutson²•Institutions (2)

University of Rochester¹, Stanford University²

01 Jan 2010-Neuropsychopharmacology

TL;DR: It is shown that human functional and structural imaging results map increasingly close to primate anatomy, and advances in neuroimaging techniques allow better spatial and temporal resolution.

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3,026 citations

Cites background from "Neural systems of reinforcement for..."

...Indeed, cells in the dorsal striatum are progressively recruited during different types of learning from simple motor tasks to drug self-administration (Everitt and Robbins, 2005; Lehericy et al, 2005; Pasupathy and Miller, 2005; Porrino et al, 2004; Volkow et al, 2006)....
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Journal Article•DOI•

NEURAL MECHANISMS OF ADDICTION: The Role of Reward-Related Learning and Memory

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Steven E. Hyman¹, Robert C. Malenka², Eric J. Nestler³•Institutions (3)

Harvard University¹, Stanford University², University of Texas Southwestern Medical Center³

15 Jun 2006-Annual Review of Neuroscience

TL;DR: Progress in identifying candidate mechanisms of addiction is reviewed, including molecular and cellular mechanisms that underlie long-term associative memories in several forebrain circuits (involving the ventral and dorsal striatum and prefrontal cortex) that receive input from midbrain dopamine neurons.

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Abstract: Addiction is a state of compulsive drug use; despite treatment and other attempts to control drug taking, addiction tends to persist. Clinical and laboratory observations have converged on the hypothesis that addiction represents the pathological usurpation of neural processes that normally serve reward-related learning. The major substrates of persistent compulsive drug use are hypothesized to be molecular and cellular mechanisms that underlie long-term associative memories in several forebrain circuits (involving the ventral and dorsal striatum and prefrontal cortex) that receive input from midbrain dopamine neurons. Here we review progress in identifying candidate mechanisms of addiction.

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2,406 citations

Cites background from "Neural systems of reinforcement for..."

...…and withdrawal, but rather long-term associative memory processes occurring in several neural circuits that receive input from midbrain dopamine neurons (Wikler & Pescor 1967, Tiffany 1990, O’Brien et al. 1998, Berke & Hyman 2000, Robbins & Everitt 2002, Everitt & Robbins 2005, Hyman 2005)....
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...These associations are presumably stored as alterations in synaptic weights and, ultimately, for the very long term, by physical remodeling of synaptic connections (Berke & Hyman 2000, Hyman & Malenka 2001)....
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...This convergence suggests neurons have a finite repertoire of molecular mecha- nisms for encoding information and that the behavioral consequences of any given alteration depends on the precise neural circuits in which it occurs (Berke & Hyman 2000, Hyman & Malenka 2001, Nestler 2002)....
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...…explain the encoding of specific cues, their overvaluation in PFC, and their connection with specific prepotent drug-seeking behaviors that develop over time and depend on the dorsal striatum (Tiffany 1990, Berke & Hyman 2000, Everitt et al. 2001, Everitt & Robbins 2005, Vanderschuren et al. 2005)....
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...Thus if drugs are readily available, automatic cue-initiated behaviors (more akin to strong habits) may play a more central role than conscious craving (Tiffany 1990, Tiffany & Carter 1998, Everitt & Robbins 2005)....
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Journal Article•DOI•

The debate over dopamine’s role in reward: the case for incentive salience

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Kent C. Berridge¹•Institutions (1)

University of Michigan¹

02 Mar 2007-Psychopharmacology

TL;DR: Dopamine’s contribution appears to be chiefly to cause ‘wanting’ for hedonic rewards, more than ‘liking’ or learning for those rewards.

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Abstract: Introduction Debate continues over the precise causal contribution made by mesolimbic dopamine systems to reward. There are three competing explanatory categories: ‘liking’, learning, and ‘wanting’. Does dopamine mostly mediate the hedonic impact of reward (‘liking’)? Does it instead mediate learned predictions of future reward, prediction error teaching signals and stamp in associative links (learning)? Or does dopamine motivate the pursuit of rewards by attributing incentive salience to reward-related stimuli (‘wanting’)? Each hypothesis is evaluated here, and it is suggested that the incentive salience or ‘wanting’ hypothesis of dopamine function may be consistent with more evidence than either learning or ‘liking’. In brief, recent evidence indicates that dopamine is neither necessary nor sufficient to mediate changes in hedonic ‘liking’ for sensory pleasures. Other recent evidence indicates that dopamine is not needed for new learning, and not sufficient to directly mediate learning by causing teaching or prediction signals. By contrast, growing evidence indicates that dopamine does contribute causally to incentive salience. Dopamine appears necessary for normal ‘wanting’, and dopamine activation can be sufficient to enhance cue-triggered incentive salience. Drugs of abuse that promote dopamine signals short circuit and sensitize dynamic mesolimbic mechanisms that evolved to attribute incentive salience to rewards. Such drugs interact with incentive salience integrations of Pavlovian associative information with physiological state signals. That interaction sets the stage to cause compulsive ‘wanting’ in addiction, but also provides opportunities for experiments to disentangle ‘wanting’, ‘liking’, and learning hypotheses. Results from studies that exploited those opportunities are described here.

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2,161 citations

Cites background or result from "Neural systems of reinforcement for..."

...Dopamine activation potently magnifies conditioned reinforcement (Everitt et al. 1999; Everitt and Robbins 2005)....
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...Originally, incentive salience probably evolved to mediate motivation for a few unconditioned rewards, but today, most often acts to add incentive value to learned Pavlovian conditioned stimuli that predict a wide variety of learned rewards (Berridge and Robinson 1998; Dayan and Balleine 2002; Elliott et al. 2003; Everitt and Robbins 2005; Hyman and Malenka 2001; Ikemoto and Panksepp 1999; Insel 2003; Kelley et al. 2005b; McClure et al. 2003; Robinson and Berridge 1993; Volkow et al. 2002b)....
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...After all, many pleasant rewards activate mesolimbic dopamine systems, ranging from food, sex, and drugs to social and cognitive rewards (Aragona et al. 2006; Becker et al. 2001; Everitt and Robbins 2005; Fiorino et al. 1997; Koob and Le Moal 2006; Roitman et al. 2004; Small et al. 2003; Thut et al. 1997; Volkow and Wise 2005; Wise 1982, 1985)....
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...These consolidation effects appear related to the consolidation effects that have been well documented for norepinephrine, stress hormones, and certain other neurochemical modulators (Dalley et al. 2005; Everitt and Robbins 2005; McGaugh 2002; Smith-Roe and Kelley 2000)....
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...…an earned UCS earning (e.g., some seeking–taking paradigms) the addition of CS ‘wanting’ motivates behavior more strongly than the UCS would alone, and dopamine manipulations effectively modulate the cue-induced enhancement of motivation for reward (Di Ciano et al. 2003; Everitt and Robbins 2005)....
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Journal Article•DOI•

The role of the basal ganglia in habit formation

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Henry H. Yin¹, Barbara J. Knowlton²•Institutions (2)

National Institutes of Health¹, University of California, Los Angeles²

01 Jun 2006-Nature Reviews Neuroscience

TL;DR: Recent work combining modern behavioural assays and neurobiological analysis of the basal ganglia has begun to yield insights into the neural basis of habit formation.

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Abstract: Many organisms, especially humans, are characterized by their capacity for intentional, goal-directed actions. However, similar behaviours often proceed automatically, as habitual responses to antecedent stimuli. How are goal-directed actions transformed into habitual responses? Recent work combining modern behavioural assays and neurobiological analysis of the basal ganglia has begun to yield insights into the neural basis of habit formation.

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2,133 citations

Cites background from "Neural systems of reinforcement for..."

...Everitt and Robbins have also shown that reafferent stimuli that predict reward can initially potentiate dopamine release in the accumbens, and eventually in the dorsal striatum, which suggests that these Pavlovian motivators can affect cortico-basal ganglia networks that mediate instrumental behaviou...
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References

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Journal Article•DOI•

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

[...]

Terry E. Robinson¹, Kent C. Berridge¹•Institutions (1)

University of Michigan¹

01 Sep 1993-Brain Research Reviews

TL;DR: S sensitization of incentive salience can produce addictive behavior 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.

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6,783 citations

Journal Article•DOI•

Dopamine, learning and motivation

[...]

Roy A. Wise¹•Institutions (1)

National Institute on Drug Abuse¹

01 Jun 2004-Nature Reviews Neuroscience

TL;DR: Dopamine release in the nucleus accumbens has been linked to the efficacy of these unconditioned rewards, but dopamine release in a broader range of structures is implicated in the 'stamping-in' of memory that attaches motivational importance to otherwise neutral environmental stimuli.

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Abstract: The hypothesis that dopamine is important for reward has been proposed in a number of forms, each of which has been challenged. Normally, rewarding stimuli such as food, water, lateral hypothalamic brain stimulation and several drugs of abuse become ineffective as rewards in animals given performance-sparing doses of dopamine antagonists. Dopamine release in the nucleus accumbens has been linked to the efficacy of these unconditioned rewards, but dopamine release in a broader range of structures is implicated in the 'stamping-in' of memory that attaches motivational importance to otherwise neutral environmental stimuli.

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3,012 citations

Journal Article•DOI•

Neural systems supporting interoceptive awareness.

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Hugo D. Critchley¹, Stefan Wiens, Pia Rotshtein¹, Arne Öhman, Raymond J. Dolan¹ - Show less +1 more•Institutions (1)

University College London¹

01 Feb 2004-Nature Neuroscience

TL;DR: In right anterior insular/opercular cortex, neural activity predicted subjects' accuracy in the heartbeat detection task and local gray matter volume correlated with both interoceptive accuracy and subjective ratings of visceral awareness.

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Abstract: Influential theories of human emotion argue that subjective feeling states involve representation of bodily responses elicited by emotional events. Within this framework, individual differences in intensity of emotional experience reflect variation in sensitivity to internal bodily responses. We measured regional brain activity by functional magnetic resonance imaging (fMRI) during an interoceptive task wherein subjects judged the timing of their own heartbeats. We observed enhanced activity in insula, somatomotor and cingulate cortices. In right anterior insular/opercular cortex, neural activity predicted subjects' accuracy in the heartbeat detection task. Furthermore, local gray matter volume in the same region correlated with both interoceptive accuracy and subjective ratings of visceral awareness. Indices of negative emotional experience correlated with interoceptive accuracy across subjects. These findings indicate that right anterior insula supports a representation of visceral responses accessible to awareness, providing a substrate for subjective feeling states.

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2,972 citations

Journal Article•DOI•

Drug addiction, dysregulation of reward, and allostasis.

[...]

George F. Koob¹, Michel Le Moal²•Institutions (2)

Scripps Research Institute¹, University of Bordeaux²

01 Feb 2001-Neuropsychopharmacology

TL;DR: The view that addiction is the pathology that results from an allostatic mechanism using the circuits established for natural rewards provides a realistic approach to identifying the neurobiological factors that produce vulnerability to addiction and relapse.

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2,678 citations

"Neural systems of reinforcement for..." refers background in this paper

...Alternatively, as in the case of obsessive-compulsive disorder itself, which has similarly been associated with dysfunctional orbitofrontal-striatal circuitry, it may be necessary to postulate a source of negative reinforcement that maintains responding, for example, through opponent motivational systems also engaged by drug abus...
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Journal Article•DOI•

Drug Addiction and Its Underlying Neurobiological Basis: Neuroimaging Evidence for the Involvement of the Frontal Cortex

[...]

Rita Z. Goldstein¹, Nora D. Volkow•Institutions (1)

Brookhaven National Laboratory¹

01 Oct 2002-American Journal of Psychiatry

TL;DR: An integrated model of drug addiction that encompasses intoxication, bingeing, withdrawal, and craving is proposed, and results imply that addiction connotes cortically regulated cognitive and emotional processes, which result in the overvaluing of drug reinforcers, the undervalued of alternative rein forcers, and deficits in inhibitory control for drug responses.

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Abstract: OBJECTIVE: Studies of the neurobiological processes underlying drug addiction primarily have focused on limbic subcortical structures. Here the authors evaluated the role of frontal cortical structures in drug addiction. METHOD: An integrated model of drug addiction that encompasses intoxication, bingeing, withdrawal, and craving is proposed. This model and findings from neuroimaging studies on the behavioral, cognitive, and emotional processes that are at the core of drug addiction were used to analyze the involvement of frontal structures in drug addiction. RESULTS: The orbitofrontal cortex and the anterior cingulate gyrus, which are regions neuroanatomically connected with limbic structures, are the frontal cortical areas most frequently implicated in drug addiction. They are activated in addicted subjects during intoxication, craving, and bingeing, and they are deactivated during withdrawal. These regions are also involved in higher-order cognitive and motivational functions, such as the ability to tr...

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2,415 citations