title: Chronic ethanol drinking by alcohol-preferring rats increases the sensitivity of the posterior ventral tegmental area to the reinforcing effects of ethanol.
abstract: BACKGROUND
  The ventral tegmental area (VTA) is involved in regulating ethanol drinking, and the posterior VTA seems to be a neuroanatomical substrate that mediates the reinforcing effects of ethanol in ethanol-naive Wistar and ethanol-naive alcohol-preferring (P) rats. The objective of this study was to test the hypothesis that chronic ethanol drinking increases the sensitivity of the posterior VTA to the reinforcing effects of ethanol.
  
  
  METHODS
  Two groups of female P rats (one given water as its sole source of fluid and the other given 24-hr free-choice access to 15% ethanol and water for at least 8 weeks) were stereotaxically implanted with guide cannulae aimed at the posterior VTA. One week after surgery, rats were placed in standard two-lever (active and inactive) operant chambers and connected to the microinfusion system. Depression of the active lever produced the infusion of 100 nl of artificial cerebrospinal fluid (CSF) or ethanol. The ethanol-naive and chronic ethanol-drinking groups were assigned to subgroups to receive artificial CSF or 25, 50, 75, or 125 mg/dl of ethanol (n = 6-9/dose/group) to self-infuse (FR1 schedule) during the 4-hr sessions given every other day.
  
  
  RESULTS
  Compared with the infusions of artificial CSF, the control group reliably (p < 0.05) self-infused 75 and 125 mg/dl of ethanol but not the lower concentrations. The ethanol-drinking group had significantly (p < 0.05) higher self-infusions of 50, 75, and 125 mg/dl of ethanol than artificial CSF during the four acquisition sessions; the number of infusions of all three doses was higher in the ethanol-drinking group than in the ethanol-naive group. Both groups decreased responding on the active lever when artificial CSF was substituted for ethanol, and both groups demonstrated robust reinstatement of responding on the active lever when ethanol was restored.
  
  
  CONCLUSIONS
  Chronic ethanol drinking by P rats increased the sensitivity of the posterior VTA to the reinforcing effects of ethanol.
authors.affiliation: Institute of Psychiatric Research, Department of Psychiatry, Indiana University School of Medicine, Indiana University, 791 Union Drive, Indianapolis, IN 46202, USA. zrodd@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 / Q000235:genetics / Q000523:psychology*; D000818:Animals; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D004298:Dopamine / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D007262:Infusions, Intravenous; D051381:Rats; D012054:Reinforcement, Psychology; D017557:Ventral Tegmental Area / Q000033:anatomy & histology / Q000502:physiology*
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol; D004298:Dopamine