title: Adolescent risk taking, cocaine self-administration, and striatal dopamine signaling.
abstract: Poor decision making and elevated risk taking, particularly during adolescence, have been strongly linked to drug use; however the causal relationships among these factors are not well understood. To address these relationships, a rat model (the Risky Decision-making Task; RDT) was used to determine whether individual differences in risk taking during adolescence predict later propensity for cocaine self-administration and/or whether cocaine self-administration causes alterations in risk taking. In addition, the RDT was used to determine how risk taking is modulated by dopamine signaling, particularly in the striatum. Results from these experiments indicated that greater risk taking during adolescence predicted greater intake of cocaine during acquisition of self-administration in adulthood, and that adult cocaine self-administration in turn caused elevated risk taking that was present following 6 weeks of abstinence. Greater adolescent risk taking was associated with lower striatal D2 receptor mRNA expression, and pharmacological activation of D2/3 receptors in the ventral, but not dorsal, striatum induced a decrease in risk taking. These findings indicate that the relationship between elevated risk taking and cocaine self-administration is bi-directional, and that low striatal D2 receptor expression may represent a predisposing factor for both maladaptive decision making and cocaine use. Furthermore, these findings suggest that striatal D2 receptors represent a therapeutic target for attenuating maladaptive decision making when choices include risk of adverse consequences.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Marci R
authors.initials: MR
authors.lastname: Mitchell
authors.affiliation: Department of Psychology, University of Kentucky, Lexington, KY, USA.
authors.forename: Virginia G
authors.initials: VG
authors.lastname: Weiss
authors.affiliation: Department of Neuroscience, University of Florida College of Medicine, Gainesville, FL, USA.
authors.forename: B Sofia
authors.initials: BS
authors.lastname: Beas
authors.affiliation: 1] Department of Neuroscience, University of Florida College of Medicine, Gainesville, FL, USA [2] Department of Psychiatry, University of Florida College of Medicine, Gainesville, FL, USA.
authors.forename: Drake
authors.initials: D
authors.lastname: Morgan
authors.affiliation: 1] Department of Neuroscience, University of Florida College of Medicine, Gainesville, FL, USA [2] Department of Psychiatry, University of Florida College of Medicine, Gainesville, FL, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Bizon
authors.affiliation: 1] Department of Neuroscience, University of Florida College of Medicine, Gainesville, FL, USA [2] Department of Psychiatry, University of Florida College of Medicine, Gainesville, FL, USA [3] Department of Psychology, University of Florida, Gainesville, FL, USA.
authors.forename: Barry
authors.initials: B
authors.lastname: Setlow
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D003657:Decision Making / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D008297:Male; D019257:Quinpirole / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism*; D012309:Risk-Taking; D012646:Self Administration
chemical_list: D018491:Dopamine Agonists; D018765:Dopamine Uptake Inhibitors; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D003042:Cocaine; D004298:Dopamine