title: Selective breeding for high alcohol preference increases the sensitivity of the posterior VTA to the reinforcing effects of nicotine.
abstract: The rate of codependency for alcohol and nicotine is extremely high. Numerous studies have indicated that there is a common genetic association for alcoholism and nicotine dependency. The current experiments examined whether selective breeding for high alcohol preference in rats may be associated with increased sensitivity of the posterior ventral tegmental area (pVTA) to the reinforcing properties of nicotine. In addition, nicotine can directly bind to the serotonin-3 (5-HT3 ) receptor, which has been shown to mediate the reinforcing properties of other drugs of abuse within the pVTA Wistar rats were assigned to groups that were allowed to self-infuse 0, 10, 50, 100, 200, 400 or 800 μM nicotine in two-lever (active and inactive) operant chambers. P rats were allowed to self-infuse 0, 1, 10, 50 or 100 μM nicotine. Co-infusion of 5-HT3 receptor antagonists with nicotine into the pVTA was also determined. P rats self-infused nicotine at lower concentrations than required to support self-administration in Wistar rats. In addition, P rats received more self-infusions of 50 and 100 μM nicotine than Wistar rats; including a 5HT3 receptor antagonist (LY-278,584 or zacopride) with nicotine reduced responding on the active lever. Overall, the data support an association between selective breeding for high alcohol preference and increased sensitivity of the pVTA to the reinforcing properties of nicotine. In addition, the data suggest that activation of 5HT3 receptors may be required to maintain the local reinforcing actions of nicotine within the pVTA.
authors.affiliation: Institute of Psychiatric Research, Departments of Psychiatry & Anatomy, Indiana School of Medicine, and Department of Psychology, Purdue School of Science, Indiana University-Purdue University at Indianapolis, Indianapolis, IN, USA.
authors.forename: Sheketha R
authors.initials: SR
authors.lastname: Hauser
authors.forename: Amy L
authors.initials: AL
authors.lastname: Bracken
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Deehan
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Toalston
authors.forename: Zheng-Ming
authors.initials: ZM
authors.lastname: Ding
authors.forename: William A
authors.initials: WA
authors.lastname: Truitt
authors.forename: Richard L
authors.initials: RL
authors.lastname: Bell
authors.forename: William J
authors.initials: WJ
authors.lastname: McBride
authors.forename: Zachary A
authors.initials: ZA
authors.lastname: Rodd
mesh_terms: D000428:Alcohol Drinking / Q000503:physiopathology*; D000704:Analysis of Variance; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001947:Breeding; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D007191:Indazoles / Q000494:pharmacology; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D017208:Rats, Wistar; D044406:Receptors, Serotonin, 5-HT3 / Q000187:drug effects; D012054:Reinforcement, Psychology; D012646:Self Administration; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000494:pharmacology; D014326:Tropanes / Q000494:pharmacology; D017557:Ventral Tegmental Area / Q000187:drug effects*
chemical_list: D001549:Benzamides; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004338:Drug Combinations; D007191:Indazoles; D018722:Nicotinic Agonists; D044406:Receptors, Serotonin, 5-HT3; D058831:Serotonin 5-HT3 Receptor Antagonists; D014326:Tropanes; C061531:LY 278584; D009538:Nicotine; C055971:zacopride
keywords: Alcohol-preferring rats; intracranial self-administration; nicotine self-infusions; serotonin-3 receptors; ventral tegmental area