title: Neural correlates of high and craving during cocaine self-administration using BOLD fMRI.
abstract: Modern theories of drug dependence hold the hedonic effects of drug-taking central to understanding the motivation for compulsive drug use. Previous neuroimaging studies have begun to identify brain regions associated with acute drug effects after passive delivery. In this study, a more naturalistic model of cocaine self-administration (SA) was employed in order to identify those sites associated with drug-induced high and craving as measures of reward and motivation. Non-treatment seeking cocaine-dependent subjects chose both when and how often i.v. cocaine administration occurred within a medically supervised SA procedure. Both functional magnetic resonance imaging (fMRI) data and real-time behavioral ratings were acquired during the 1-h SA period. Drug-induced HIGH was found to correlate negatively with activity in limbic, paralimbic, and mesocortical regions including the nucleus accumbens (NAc), inferior frontal/orbitofrontal gyrus (OFC), and anterior cingulate (AC), while CRAVING correlated positively with activity in these regions. This study provides the first evidence in humans that changes in subjective state surrounding cocaine self-administration reflect neural activity of the endogenous reward system.
authors.affiliation: Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. risinger@mcw.edu
authors.forename: Robert C
authors.initials: RC
authors.lastname: Risinger
authors.forename: Betty Jo
authors.initials: BJ
authors.lastname: Salmeron
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Ross
authors.forename: Shelley L
authors.initials: SL
authors.lastname: Amen
authors.forename: Michael
authors.initials: M
authors.lastname: Sanfilipo
authors.forename: Raymond G
authors.initials: RG
authors.lastname: Hoffmann
authors.forename: Alan S
authors.initials: AS
authors.lastname: Bloom
authors.forename: Hugh
authors.initials: H
authors.lastname: Garavan
authors.forename: Elliot A
authors.initials: EA
authors.lastname: Stein
mesh_terms: D000328:Adult; D001519:Behavior / Q000187:drug effects; D001921:Brain / Q000502:physiology*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000503:physiopathology* / Q000523:psychology*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D010100:Oxygen / Q000097:blood*; D012646:Self Administration
chemical_list: D018765:Dopamine Uptake Inhibitors; D003042:Cocaine; D010100:Oxygen