title: Regional heterogeneity for the intracranial self-administration of ethanol and acetaldehyde within the ventral tegmental area of alcohol-preferring (P) rats: involvement of dopamine and serotonin.
abstract: The meso-limbic dopamine (DA) system has an important role in regulating alcohol drinking. Previous findings from our laboratory indicated that Wistar rats self-administered ethanol (EtOH) directly into the posterior, but not anterior, ventral tegmental area (VTA), and that coadministration of a DA D(2,3) receptor agonist or a serotonin-3 (5-HT3) receptor antagonist blocked EtOH self-administration. In addition, we reported that alcohol-preferring (P) rats self-administered acetaldehyde (ACD), the first metabolite of EtOH, into the posterior VTA. The objectives of this study were to compare the reinforcing effects of EtOH and ACD within the VTA of P rats to examine the possibility that the reinforcing effects of EtOH within the VTA may be mediated by its conversion to ACD. Adult female P rats were stereotaxically implanted with guide cannulae aimed at either the posterior or anterior VTA. At 1 week after surgery, rats were placed in standard two-lever (active and inactive) experimental chambers for a total of seven to eight sessions. The 4-h sessions were conducted every other day. The results indicated that (a) 75-300 mg% (17-66 mM) EtOH and 6-90 microM ACD were self-administered into the posterior, but not anterior, VTA; (b) the self-administration of 150 mg% EtOH was not altered by coinfusion of a catalase inhibitor; (c) coadministration of the D(2/3) agonist quinpirole (100 microM) blocked the self-infusions of 150 mg% EtOH and 23 microM ACD into the posterior VTA; and (d) coadministration of 200 microM ICS205,930 (5-HT3 receptor antagonist) prevented the self-infusion of 150 mg% EtOH, whereas concentrations of ICS 205,930 up to 400 microM had no effect on the self-infusion of 23 microM ACD into the posterior VTA. Overall, the results of this study indicate that EtOH and ACD can independently produce reinforcing effects within the posterior VTA, and that activation of DA neurons mediates these effects. Furthermore, activation of 5-HT3 receptors within the posterior VTA is involved in the self-infusion of EtOH, but not ACD.
authors.affiliation: Department of Psychiatry, Institute of Psychiatric Research, Indiana University-Purdue University at Indianapolis, Indianapolis, IN, 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: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: James M
authors.initials: JM
authors.lastname: Murphy
authors.forename: Avram
authors.initials: A
authors.lastname: Goldstein
authors.forename: Alejandro
authors.initials: A
authors.lastname: Zaffaroni
authors.forename: Ting-Kai
authors.initials: TK
authors.lastname: Li
authors.forename: William J
authors.initials: WJ
authors.lastname: McBride
mesh_terms: D000079:Acetaldehyde / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology*; D000428:Alcohol Drinking / Q000523:psychology*; D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D002404:Catheterization; D002492:Central Nervous System Depressants / Q000008:administration & dosage* / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D007211:Indoles / Q000494:pharmacology; D007267:Injections; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D012054:Reinforcement, Psychology; D012646:Self Administration; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013238:Stereotaxic Techniques; D000077526:Tropisetron; D017557:Ventral Tegmental Area / Q000378:metabolism
chemical_list: D002492:Central Nervous System Depressants; D018491:Dopamine Agonists; D004791:Enzyme Inhibitors; D007211:Indoles; D012702:Serotonin Antagonists; D019257:Quinpirole; D012701:Serotonin; D000431:Ethanol; D000077526:Tropisetron; D000079:Acetaldehyde; D004298:Dopamine; D000640:Amitrole