title: Prolonged increase in the sensitivity of the posterior ventral tegmental area to the reinforcing effects of ethanol following repeated exposure to cycles of ethanol access and deprivation.
abstract: The posterior ventral tegmental area (VTA) is a neuroanatomical substrate mediating the reinforcing effects of ethanol in rats. Repeated alcohol deprivations produce robust ethanol intakes of alcohol-preferring (P) rats during relapse and increase the reinforcing effects of oral alcohol self-administration. The objective of this study was to test the hypothesis that alcohol drinking and repeated alcohol deprivations will increase the reinforcing effects of ethanol within the posterior VTA of P rats. Groups of female P rats were used (alcohol-naive, continuous access, and repeatedly deprived). Each rat was implanted with a guide cannula aimed at the posterior VTA. Depression of the active lever produced the infusion of 100 nl of artificial cerebrospinal fluid (CSF) or ethanol (25-300 mg%). Each rat was given only one ethanol concentration during the 4-h sessions conducted every other day. Compared with the infusions of artificial CSF, the alcohol-naive group reliably self-infused 75 and 150 mg% ethanol, but not the lower or higher concentrations. On the other hand, the continuous access group had significantly higher self-infusions of 50, 75, 150, and 300 mg% ethanol compared with artificial CSF infusions. The repeatedly deprived group also self-infused significantly more of 50, 75, 150, and 300 mg% ethanol than artificial CSF; moreover, the number of infusions for all four concentrations was higher in the repeatedly deprived versus the continuous access group. Chronic alcohol drinking by P rats increased the reinforcing effects of ethanol within the posterior VTA, and repeated alcohol deprivations produced a further increase in these reinforcing effects of ethanol.
authors.affiliation: Institute of Psychiatric Research, Department of Psychiatry, Indiana University School of Medicine, Indianapolis, 46202, USA. Psycholzrodd@iupui.edu
authors.forename: Zachary A
authors.initials: ZA
authors.lastname: Rodd
authors.forename: Richard L
authors.initials: RL
authors.lastname: Bell
authors.forename: Victoria K
authors.initials: VK
authors.lastname: McQueen
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Davids
authors.forename: Cathleen C
authors.initials: CC
authors.lastname: Hsu
authors.forename: James M
authors.initials: JM
authors.lastname: Murphy
authors.forename: Ting-Kai
authors.initials: TK
authors.lastname: Li
authors.forename: Lawrence
authors.initials: L
authors.lastname: Lumeng
authors.forename: William J
authors.initials: WJ
authors.lastname: McBride
mesh_terms: D000428:Alcohol Drinking / Q000523:psychology*; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D051381:Rats; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D017557:Ventral Tegmental Area / Q000033:anatomy & histology / Q000187:drug effects*
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol