title: A switch in the neuromodulatory effects of dopamine in the oval bed nucleus of the stria terminalis associated with cocaine self-administration in rats.
abstract: Chronic exposure to drugs of abuse alters brain reward circuits and produces functional changes in the dopamine (DA) system. However, it is not known whether these changes are directly related to drug-driven behaviors or whether they simply are adaptive responses to long-term drug exposure. Here, we combined the rat model of cocaine self-administration with brain slice electrophysiology to identify drug-use related alterations in the neuromodulatory effects of DA in the oval bed nucleus of the stria terminalis (ovBST), a robust DA terminal field. Long-Evans rats self-administered cocaine intravenously (0.75 mg/kg/injection) for an average of 15 d, on reward-lean or -rich schedules of reinforcement. Brain slice recordings conducted 20 h after the last self-administration session revealed a reversal of the neuromodulatory effect of DA on GABA(A)-IPSCs. Specifically, the effect of DA switched from a D2-mediated decrease in drug-naive rats to a D1-receptor-mediated increase in GABA(A)-IPSC in cocaine self-administering rats. Furthermore, the switch in DA modulation of GABA(A)-IPSC remained after a 30 d withdrawal period. In contrast, this switch was not observed after the acquisition phase of cocaine self-administration, when rats received cocaine passively, or in rats maintaining sucrose self-administration. Therefore, our study reveals a reversal in the effects of DA on inhibitory transmission, from reduction to enhancement, in the ovBST of cocaine self-administering rats. This change was unique to voluntary intake of cocaine and maintained after a withdrawal period, suggesting a mechanism underlying the maintenance of cocaine self-administration and perhaps craving during drug-free periods.
authors.affiliation: Department of Anesthesiology and Perioperative Medicine, Center for Neuroscience Studies, Queen's University, Kingston, Ontario K7L 3N6, Canada.
authors.forename: Michal
authors.initials: M
authors.lastname: Krawczyk
authors.forename: Robyn
authors.initials: R
authors.lastname: Sharma
authors.forename: Xenos
authors.initials: X
authors.lastname: Mason
authors.forename: Julian
authors.initials: J
authors.lastname: Debacker
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Jones
authors.forename: Eric C
authors.initials: EC
authors.lastname: Dumont
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects; D004298:Dopamine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011810:Quinoxalines / Q000494:pharmacology; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D012055:Reinforcement Schedule; D012646:Self Administration; D012686:Septal Nuclei / Q000187:drug effects*; D055366:Synaptic Potentials / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D018691:Excitatory Amino Acid Antagonists; D018377:Neurotransmitter Agents; D011810:Quinoxalines; C534628:SCH 23390; D019257:Quinpirole; D015016:Yohimbine; C056723:FG 9041; C067113:SK&F 81297; D003042:Cocaine; D004298:Dopamine; D009638:Norepinephrine