Cocaine addiction is characterized by impulsivity, impaired social relationships, and abnormal mesocorticolimbic reward processing, but their interrelationships relative to stages of cocaine addiction are unclear. We assessed blood-oxygenation-level dependent (BOLD) signal in ventral and dorsal striatum during functional magnetic resonance imaging (fMRI) in current (CCD; n = 30) and former (FCD; n = 28) cocaine dependent subjects as well as healthy control (HC; n = 31) subjects while playing an interactive competitive Domino game involving risk-taking and reward/punishment processing. Out-of-scanner impulsivity-related measures were also collected. Although both FCD and CCD subjects scored significantly higher on impulsivity-related measures than did HC subjects, only FCD subjects had differences in striatal activation, specifically showing hypoactivation during their response to gains versus losses in right dorsal caudate, a brain region linked to habituation, cocaine craving and addiction maintenance. Right caudate activity in FCD subjects also correlated negatively with impulsivity-related measures of self-reported compulsivity and sensitivity to reward. These findings suggest that remitted cocaine dependence is associated with striatal dysfunction during social reward processing in a manner linked to compulsivity and reward sensitivity measures. Future research should investigate the extent to which such differences might reflect underlying vulnerabilities linked to cocaine-using propensities (e.g., relapses).
|State||Published - May 14 2012|
Bibliographical noteFunding Information:
Dr. Potenza has consulted for and advised Boehringer Ingelheim; has consulted for and has financial interests in Somaxon; has received research support from the Veteran’s Administration, Mohegan Sun Casino, the National Center for Responsible Gaming and its affiliated Institute for Research on Gambling Disorders, and Forest Laboratories, Psyadon, Ortho-McNeil, Oy-Control/Biotie and Glaxo-SmithKline pharmaceuticals; has participated in surveys, mailings or telephone consultations related to drug addiction, impulse control disorders or other health topics; has consulted for law offices and the federal public defender’s office in issues related to impulse control disorders; provides clinical care in the Connecticut Department of Mental Health and Addiction Services Problem Gambling Services Program; has performed grant reviews for the National Institutes of Health and other agencies; has guest-edited journal sections; has given academic lectures in grand rounds, CME events and other clinical or scientific venues; and has generated books or book chapters for publishers of mental health texts. Dr. Krystal’s conflicts of interest are as follows: 1) Consultant for Aisling Capital, LLC, AstraZeneca Pharmaceuticals, Brintnall & Nicolini, Inc., Easton Associates, Gilead Sciences, Inc., GlaxoSmithKline, Janssen Pharmaceuticals, Lundbeck Research USA, Merz Pharmaceuticals, MK Medical Communications, Medivation, Inc., Naurex, Inc., Pfizer Pharmaceuticals, and Teva Pharmaceutical Industries, Ltd.; 2) Scientific advisory board/consultant for Abbott Laboratories, Bristol-Myers Squibb, Eli Lilly and Co., Lohocla Research Corporation, SK Holdings Co. Ltd., Takeda Industries, and Transcept Pharmaceuticals; 3) Exercizable warrant options for Tetragenex Pharmaceuticals (value less than $100); 4) Research support to Department of Veterans Affairs for Janssen Research Foundation (provided drug and some study support to the Department of Veterans Affairs); 5) Derives income greater than $10,000 as the Editor of Biological Psychiatry; 6) Board Of Directors for the Coalition for Translational Research in Alcohol and Substance Use Disorders; 7) President-Elect for the American College of Neuropsychopharmacology; and 8) has the following patents and inventions: Seibyl JP, Krystal JH, Charney DS. Dopamine and noradrenergic reuptake inhibitors in treatment of schizophrenia. Patent #:5,447,948. September 5, 1995; co-inventor with Dr. Gerard Sanacora on a filed patent application by Yale University related to targeting the glutamatergic system for the treatment of neuropsychiatric disorders (PCTWO06108055A1); and Intranasal Administration of ketamine to Treat Depression (pending). These potential competing interests do not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials. None of the research support listed above was used for this particular study.
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