title: Sensitization of ventral tegmental area dopamine neurons to the stimulating effects of ethanol.
abstract: BACKGROUND
  Previous studies indicated that chronic alcohol drinking increased the sensitivity of the posterior ventral tegmental area (p-VTA) to the reinforcing effects of ethanol. The current study tested the hypothesis that local exposure of the p-VTA to ethanol would increase the sensitivity of dopamine (DA) neurons to the stimulating effects of ethanol.
  
  
  METHODS
  Experiment 1 examined the stimulating effects of ethanol in the p-VTA after a 7-day ethanol pretreatment in the p-VTA. Adult female Wistar rats were pretreated with microinjections of 200 mg% ethanol or artificial cerebrospinal fluid (aCSF) into the p-VTA once a day for 7 days. On the eighth day, rats received a challenge injection of ethanol (100, 200, or 300 mg%) or aCSF into the p-VTA, and extracellular DA levels were measured in the nucleus accumbens (NAc) shell with microdialysis. Experiment 2 examined the stimulating effects of ethanol (200 mg%) after a 3- or 5-day ethanol (200 mg%) pretreatment in the p-VTA. Experiment 3 examined the stimulating effects of ethanol (200 mg%) 7 days after the last of the 7-day ethanol (200 mg%) pretreatments in the p-VTA.
  
  
  RESULTS
  Experiment 1: in both aCSF- and ethanol-pretreated rats, the challenge microinjection of ethanol dose-dependently increased DA release in the NAc shell, with significantly greater increases in ethanol-pretreated groups. Experiment 2: the 5-day, but not 3-day, ethanol pretreatment protocol increased the response of p-VTA dopamine neurons to the ethanol challenge. Experiment 3: the increased stimulating effects of ethanol were still evident after 7 days.
  
  
  CONCLUSIONS
  The results indicate that repeated local ethanol exposure of the p-VTA produced neuroadaptations in DA neurons projecting to the NAc shell, resulting in a persistent increase in the sensitivity of these neurons to the stimulating effects of ethanol.
authors.affiliation: Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN 46202-4887, USA. zding@iupui.edu
authors.forename: Zheng-Ming
authors.initials: ZM
authors.lastname: Ding
authors.forename: Zachary A
authors.initials: ZA
authors.lastname: Rodd
authors.forename: Eric A
authors.initials: EA
authors.lastname: Engleman
authors.forename: William J
authors.initials: WJ
authors.lastname: McBride
mesh_terms: D000818:Animals; D019540:Area Under Curve; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D017248:Enzyme Multiplied Immunoassay Technique; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005260:Female; D017551:Microdialysis; D008845:Microinjections; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013238:Stereotaxic Techniques; D013268:Stimulation, Chemical; D017557:Ventral Tegmental Area / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol; D004298:Dopamine