title: Acute effects of cocaine and cannabis on reversal learning as a function of COMT and DRD2 genotype.
abstract: BACKGROUND
  Long-term cannabis and cocaine use has been associated with impairments in reversal learning. However, how acute cannabis and cocaine administration affect reversal learning in humans is not known.
  
  
  OBJECTIVE
  In this study, we aimed to establish the acute effects of administration of cannabis and cocaine on valence-dependent reversal learning as a function of DRD2 Taq1A (rs1800497) and COMT Val108/158Met (rs4680) genotype.
  
  
  METHODS
  A double-blind placebo-controlled randomized 3-way crossover design was used. Sixty-one regular poly-drug users completed a deterministic reversal learning task under the influence of cocaine, cannabis, and placebo that enabled assessment of both reward- and punishment-based reversal learning.
  
  
  RESULTS
  Proportion correct on the reversal learning task was increased by cocaine, but decreased by cannabis. Effects of cocaine depended on the DRD2 genotype, as increases in proportion correct were seen only in the A1 carriers, and not in the A2/A2 homozygotes. COMT genotype did not modulate drug-induced effects on reversal learning.
  
  
  CONCLUSIONS
  These data indicate that acute administration of cannabis and cocaine has opposite effects on reversal learning. The effects of cocaine, but not cannabis, depend on interindividual genetic differences in the dopamine D2 receptor gene.
authors.affiliation: Department of Psychiatry, Radboud university medical center, Nijmegen, The Netherlands. desireespronk@gmail.com.|Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands. desireespronk@gmail.com.
authors.forename: Desirée B
authors.initials: DB
authors.lastname: Spronk
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.|Expert Center for Chronic Fatigue, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Marieke E
authors.initials: ME
authors.lastname: Van der Schaaf
authors.affiliation: Department of Psychiatry, Radboud university medical center, Nijmegen, The Netherlands.|Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
authors.forename: Roshan
authors.initials: R
authors.lastname: Cools
authors.affiliation: Department of Clinical Psychology, Leiden Institute for Brain and Cognition, Leiden University, Leiden, The Netherlands.
authors.forename: Ellen R A
authors.initials: ER
authors.lastname: De Bruijn
authors.affiliation: Department of Psychiatry, Radboud university medical center, Nijmegen, The Netherlands.|Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.|Department of Human Genetics, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Barbara
authors.initials: B
authors.lastname: Franke
authors.affiliation: Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands.
authors.forename: Janelle H P
authors.initials: JH
authors.lastname: van Wel
authors.affiliation: Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands.
authors.forename: Johannes G
authors.initials: JG
authors.lastname: Ramaekers
authors.affiliation: Department of Psychiatry, Radboud university medical center, Nijmegen, The Netherlands.|Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.|Pompestichting for Forensic Psychiatry, Nijmegen, The Netherlands.|Department of Criminal Law and Criminology, Radboud University, Nijmegen, The Netherlands.
authors.forename: Robbert J
authors.initials: RJ
authors.lastname: Verkes
mesh_terms: D000293:Adolescent; D000328:Adult; D001288:Attention / Q000187:drug effects; D002188:Cannabis; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003042:Cocaine / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D011678:Punishment; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D012193:Reversal Learning / Q000187:drug effects*; D012201:Reward; D019966:Substance-Related Disorders / Q000523:psychology; D055815:Young Adult
chemical_list: C581293:DRD2 protein, human; D017448:Receptors, Dopamine D2; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase; D003042:Cocaine
keywords: COMT Val108/158Met; Cannabis; Cocaine; DRD2 Taq1A; Human; Individual differences; Polymorphism; Reversal learning; THC