Background The capacity of drug cues to elicit drug-seeking behavior is believed to play a fundamental role in drug dependence; yet the neurofunctional basis of human drug cue-reactivity is not fully understood. We performed a meta-analysis to identify brain regions that are consistently activated by presentation of drug cues. Studies involving treatment-seeking and nontreatment-seeking substance users were contrasted to determine whether there were consistent differences in the neural response to drug cues between these populations. Finally, to assess the neural basis of craving, consistency across studies in brain regions that show correlated activation with craving was assessed. Methods Appropriate studies, assessing the effect of drug-related cues or manipulations of drug craving in drug-user populations across the whole brain, were obtained via the PubMed database and literature search. Activation likelihood estimation, a method of quantitative meta-analysis that estimates convergence across experiments by modeling the spatial uncertainty of neuroimaging data, was used to identify consistent regions of activation. Results Cue-related activation was observed in the ventral striatum (across both subgroups), amygdala (in the treatment-seeking subgroup and overall), and orbitofrontal cortex (in the nontreatment-seeking subgroup and overall) but not insula cortex. Although a different pattern of frontal and temporal lobe activation between the subgroups was observed, these differences were not significant. Finally, right amygdala and left middle frontal gyrus activity were positively associated with craving. Conclusions These results substantiate the key neural substrates underlying reactivity to drug cues and drug craving.

Dual-process theories of learning and addiction propose that whereas freely elected drug/reward-seeking is goal-directed in being mediated by the expected value of the outcome, cue-elicited drug/reward-seeking is habitual in being elicited directly by antecedent stimuli, without retrieving a representation of outcome value. To substantiate this claim, the current study conducted a human devaluation-transfer procedure in which young adult smokers were first trained on a concurrent choice task to earn tobacco and chocolate points before one outcome was devalued by specific satiety or health warnings against consumption of that outcome. When choice was again tested in extinction, the selective reduction in performance of the action associated with the devalued outcome indicated that choice was controlled by an expectation of outcome value, that is, was goal-directed. Moreover, the presentation of tobacco and chocolate cues enhanced selection of the response associated with that outcome, indicating that transfer was also mediated by the retrieval of the outcome representation. Paradoxically, however, the magnitude of this transfer effect was unaffected by devaluation, indicating that the stimulus retrieved a representation of outcome identity but not current incentive value. Individual differences in tobacco dependence in the young adult sample were associated with tobacco preference in the concurrent choice task but not with the devaluation or transfer effects. These data accord with dual-process theories in suggesting that drug/reward-seeking are mediated by goal-directed and habitual controllers under freely elected and cued conditions, respectively, and that initial uptake of drug use is associated with hyper-valuation of the drug as an outcome of goal-directed drug-seeking rather than with accelerated habit formation.

The proposed theoretical synthesis may account for the contributions of appetitive and aversive motivational processes involved in self-regulatory conflicts to AB, and it yields testable predictions about the conditions under which AB should predict and have a causal influence on future consummatory behavior. This has implications for the prediction and modification of unhealthy behaviors and associated disorders. (PsycINFO Database Record

According to contemporary learning theory, drug-seeking behaviour reflects the summation of two dissociable controllers. Whereas goal-directed drug-seeking is determined by the expected current incentive value of the drug, stimulus-elicited drug-seeking is determined by the expected probability of the drug independently of its current incentive value, and these two controllers contribute additively to observed drug-seeking. One applied prediction of this model is that smoking cessation pharmacotherapies selectively attenuate tonic but not cueelicited craving because they downgrade the expected incentive value of the drug but leave expected probability intact. To test this, the current study examined whether nicotine replacement therapy (NRT) nasal spray would modify goal-directed tobacco choice in a human outcome devaluation procedure, but leave cue-elicited tobacco choice in a Pavlovian to instrumental transfer (PIT) procedure intact. Smokers (n=96) first underwent concurrent choice training in which two responses earned tobacco or chocolate points respectively.Participants then ingested either NRT nasal spray (1mg) or chocolate (147g) to devalue one outcome. Concurrent choice was then tested again in extinction to measure goal-directed control of choice, and in a PIT test to measure the extent to which tobacco and chocolate stimuli enhanced choice of the same outcome. It was found that NRT modified tobacco choice in the extinction test but not the extent to which the tobacco stimulus enhanced choice of the tobacco outcome in the PIT test. This dissociation suggests that the propensity to engage in drug-seeking is determined independently by the expected value and probability of the drug, and that the partial efficacy of pharmacotherapy is due to its selective effect on expected drug value.

Learning theory proposes that drug seeking is a synthesis of multiple controllers. Whereas goal-directed drug seeking is determined by the anticipated incentive value of the drug, habitual drug seeking is elicited by stimuli that have formed a direct association with the response. Moreover, drug-paired stimuli can transfer control over separately trained drug seeking responses by retrieving an expectation of the drug's identity (specific transfer) or incentive value (general transfer). This review covers outcome devaluation and transfer of stimulus-control procedures in humans and animals, which isolate the differential governance of drug seeking by these four controllers following various degrees of contingent and noncontingent drug exposure. The neural mechanisms underpinning these four controllers are also reviewed. These studies suggest that although initial drug seeking is goal-directed, chronic drug exposure confers a progressive loss of control over action selection by specific outcome representations (impaired outcome devaluation and specific transfer), and a concomitant increase in control over action selection by antecedent stimuli (enhanced habit and general transfer). The prefrontal cortex and mediodorsal thalamus may play a role in this drug-induced transition to behavioral autonomy.

Background and Aims Despite decades of research on co-occurring smoking and depression, cessation rates remain consistently lower for depressed smokers than for smokers in the general population, highlighting the need for theory-driven models of smoking and depression. This paper provides a systematic review with a particular focus on psychological states that disproportionately motivate smoking in depression, and frame an incentive learning theory account of smoking-depression co-occurrence. Methods We searched PubMed, Scopus, PsychINFO, and CINAHL through December 2014, which yielded 852 articles. Using pre-established eligibility criteria, we identified papers focused on clinical issues and motivational mechanisms underlying smoking in established, adult smokers (i.e., maintenance, quit attempts, and cessation/relapse) with elevated symptoms of depression. Two reviewers independently determined whether articles met review criteria. We included 297 articles in qualitative synthesis. Results Our review identified three primary mechanisms that underlie persistent smoking among depressed smokers: low positive affect, high negative affect, and cognitive impairment. We propose a novel application of incentive learning theory which posits that depressed smokers experience greater increases in the expected value of smoking in the face of these three motivational states, which promotes goal-directed choice of smoking behavior over alternative actions. Conclusions The incentive learning theory accounts for current evidence on how depression primes smoking behavior and provides a unique framework for conceptualizing psychological mechanisms of smoking maintenance among depressed smokers. Treatment should focus on correcting adverse internal states, and beliefs about the high value of smoking in those states, to improve cessation outcomes for depressed smokers.

According to incentive salience theory, conditioned stimuli (CS+) associated with drug reinforcement acquire the capacity to elicit a conditioned attentional orienting response, which controls drug-seeking and drug-taking behaviour. We sought evidence for this proposal by measuring visual attentional orienting towards smoking pictures presented briefly in the periphery of the visual field, versus control pictures likewise presented, in smokers versus non-smokers. In each trial, smokers and non-smokers responded manually to a dot probe stimulus that appeared in a location previously occupied by either a smoking picture or a control picture. Attentional bias scores were calculated by subtracting the median reaction time (RT) in the former condition from the median RT in the latter condition. In two experiments, light-smokers (smokers of fewer than 20 cigarettes/day) produced a mean bias score that was significantly greater than that of heavy-smokers (smokers of 20 or more cigarettes/day) and non-smokers. In addition, when smokers from the two experiments were pooled, a significant quadratic relationship was found between cigarettes/day and the attentional bias for the smoking stimuli. These findings are consistent with incentive salience theories and dual-process theories of addiction.

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