title: Intracranial self-administration of ethanol within the ventral tegmental area of male Wistar rats: evidence for involvement of dopamine neurons.
abstract: Previous work from our laboratory indicated that female Wistar rats will self-administer ethanol (EtOH) directly into the posterior ventral tegmental area (VTA). These results suggested that VTA dopamine (DA) neurons might be involved in mediating the reinforcing actions of EtOH within this region. The objectives of this study were to determine (1) the dose-response effects for the self-administration of EtOH into the VTA of male Wistar rats, and (2) the involvement of VTA DA neurons in the reinforcing actions of EtOH within the VTA. Adult male Wistar rats were implanted stereotaxically with guide cannulas aimed at the posterior or anterior VTA. After 1 week, rats were placed in standard two-lever (active and inactive) experimental chambers for a total of seven to eight sessions. The first experiment determined the intracranial self-administration of EtOH (0-400 mg%) into the posterior and anterior VTA. The second experiment examined the effects of coadministration of the D2/3 agonist quinpirole on the acquisition and maintenance of EtOH self-infusions into the posterior VTA. The final experiment determined the effects of a D2 antagonist (sulpiride) to reinstate self-administration behavior in rats given EtOH and quinpirole to coadminister. Male Wistar rats self-infused 100-300 mg% EtOH directly into the posterior, but not anterior, VTA. Coadministration of quinpirole prevented the acquisition and extinguished the maintenance of EtOH self-infusion into the posterior VTA, and addition of sulpiride reinstated EtOH self-administration. The results of this study indicate that EtOH is reinforcing within the posterior VTA of male Wistar rats and suggest that activation of VTA DA neurons is involved in this process.
authors.affiliation: Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. zrodd@iupui.edu
authors.forename: Zachary A
authors.initials: ZA
authors.lastname: Rodd
authors.forename: Roberto I
authors.initials: RI
authors.lastname: Melendez
authors.forename: Richard L
authors.initials: RL
authors.lastname: Bell
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Kuc
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: James M
authors.initials: JM
authors.lastname: Murphy
authors.forename: William J
authors.initials: WJ
authors.lastname: McBride
mesh_terms: D019973:Alcohol-Related Disorders / Q000503:physiopathology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D005108:Extinction, Psychological / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012054:Reinforcement, Psychology; D012646:Self Administration; D012737:Sex Factors; D013469:Sulpiride / Q000494:pharmacology; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000378:metabolism
chemical_list: D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D019257:Quinpirole; D000431:Ethanol; D013469:Sulpiride; D004298:Dopamine