title: Dissociable Effects of Cocaine Dependence on Reward Processes: The Role of Acute Cocaine and Craving.
abstract: The relative impact of chronic vs acute cocaine on dependence-related variability in reward processing in cocaine-dependent individuals (CD) is not well understood, despite the relevance of such effects to long-term outcomes. To dissociate these effects, CD (N=15) and healthy controls (HC; N=15) underwent MRI two times while performing a monetary incentive delay task. Both scans were identical across subjects/groups, except that, in a single-blind, counterbalanced design, CD received intravenous cocaine (30 mg/70 kg) before one session (CD+cocaine) and saline in another (CD+saline). Imaging analyses focused on activity related to anticipatory valence (gain/loss), anticipatory magnitude (small/medium/large), and reinforcing outcomes (successful/unsuccessful). Drug condition (cocaine vs saline) and group (HC vs CD+cocaine or CD+saline) did not influence valence-related activity. However, compared with HC, magnitude-related activity for gains was reduced in CD in the left cingulate gyrus post-cocaine and in the left putamen in the abstinence/saline condition. In contrast, magnitude-dependent activity for losses increased in CD vs HC in the right inferior parietal lobe post-cocaine and in the left superior frontal gyrus post-saline. Across outcomes (ie, successful and unsuccessful) activity in the right habenula decreased in CD in the abstinence/saline condition vs acute cocaine and HC. Cocaine-dependent variability in outcome- and loss-magnitude activity correlated negatively with ratings of cocaine craving and positively with how high subjects felt during the scanning session. Collectively, these data suggest dissociable effects of acute cocaine on non-drug reward processes, with cocaine consumption partially ameliorating dependence-related insensitivity to reinforcing outcomes/'liking', but having no discernible effect on dependence-related alterations in incentive salience/'wanting'. The relationship of drug-related affective sequelae to non-drug reward processing suggests that CD experience a general alteration of reward function and may be motivated to continue using cocaine for reasons beyond desired drug-related effects. This may have implications for individual differences in treatment efficacy for approaches that rely on reinforcement strategies (eg, contingency management) and for the long-term success of treatment.
authors.affiliation: Neuroimaging Research Branch, National Institute on Drug Abuse-Intramural Research Program, NIH, Baltimore, MD, USA.|Program for Translational Research on Adversity and Neurodevelopment, Bennett Pierce Prevention Research Center, Health and Human Development, The Pennsylvania State University, University Park, PA, USA.
authors.forename: Emma Jane
authors.initials: EJ
authors.lastname: Rose
authors.affiliation: Neuroimaging Research Branch, National Institute on Drug Abuse-Intramural Research Program, NIH, Baltimore, MD, USA.
authors.forename: Betty Jo
authors.initials: BJ
authors.lastname: Salmeron
authors.affiliation: Neuroimaging Research Branch, National Institute on Drug Abuse-Intramural Research Program, NIH, Baltimore, MD, USA.
authors.forename: Thomas J
authors.identifier: 0000-0002-7745-3572
authors.initials: TJ
authors.lastname: Ross
authors.affiliation: Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: James
authors.identifier: 0000-0002-9236-3719
authors.initials: J
authors.lastname: Waltz
authors.affiliation: MIND Institute, Department of Psychiatry and Behavioral Sciences, University of California Davis School of Medicine, Sacramento, CA, USA.
authors.forename: Julie B
authors.initials: JB
authors.lastname: Schweitzer
authors.affiliation: Neuroimaging Research Branch, National Institute on Drug Abuse-Intramural Research Program, NIH, Baltimore, MD, USA.
authors.forename: Elliot A
authors.initials: EA
authors.lastname: Stein
mesh_terms: D000328:Adult; D059031:Anticipation, Psychological / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000000981:diagnostic imaging / Q000503:physiopathology*; D066249:Craving / Q000187:drug effects / Q000502:physiology*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D012201:Reward
chemical_list: D018765:Dopamine Uptake Inhibitors; D003042:Cocaine