title: Gene x abstinence effects on drug cue reactivity in addiction: multimodal evidence.
abstract: Functional polymorphisms in the dopamine transporter gene (DAT1 or SLC6A3) modulate responsiveness to salient stimuli, such that carriers of one 9R-allele of DAT1 (compared with homozygote carriers of the 10R-allele) show heightened reactivity to drug-related reinforcement in addiction. Here, using multimodal neuroimaging and behavioral dependent variables in 73 human cocaine-addicted individuals and 47 healthy controls, we hypothesized and found that cocaine-addicted carriers of a 9R-allele exhibited higher responses to drug cues, but only among individuals who had used cocaine within 72 h of the study as verified by positive cocaine urine screens (a state characterized by intense craving). Importantly, this responsiveness to drug cues was reliably preserved across multimodal imaging and behavioral probes: psychophysiological event-related potentials, self-report, simulated cocaine choice, and fMRI. Because drug cues contribute to relapse, our results identify the DAT1R 9R-allele as a vulnerability allele for relapse especially during early abstinence (e.g., detoxification).
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Moeller
authors.forename: Muhammad A
authors.initials: MA
authors.lastname: Parvaz
authors.forename: Elena
authors.initials: E
authors.lastname: Shumay
authors.forename: Nicasia
authors.initials: N
authors.lastname: Beebe-Wang
authors.forename: Anna B
authors.initials: AB
authors.lastname: Konova
authors.forename: Nelly
authors.initials: N
authors.lastname: Alia-Klein
authors.forename: Nora D
authors.initials: ND
authors.lastname: Volkow
authors.forename: Rita Z
authors.initials: RZ
authors.lastname: Goldstein
mesh_terms: D000328:Adult; D000483:Alleles; D000704:Analysis of Variance; D016739:Behavior, Addictive / Q000235:genetics; D001921:Brain / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology*; D001931:Brain Mapping; D002755:Choice Behavior; D003042:Cocaine / Q000652:urine; D019970:Cocaine-Related Disorders / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology* / Q000652:urine; D003463:Cues; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D004569:Electroencephalography; D004644:Emotions / Q000502:physiology; D005071:Evoked Potentials / Q000502:physiology; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D010775:Photic Stimulation; D011601:Psychophysics; D012054:Reinforcement, Psychology
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human; D003042:Cocaine; D010100:Oxygen