Selective breeding for high alcohol preference increases the sensitivity of the posterior VTA to the reinforcing effects of nicotine

Sheketha R. Hauser, Amy L. Bracken, Gerald A. Deehan, Jamie E. Toalston, Zheng Ming Ding, William A. Truitt, Richard L. Bell, William J. McBride, Zachary A. Rodd

Research output: Contribution to journalArticle

21 Scopus citations

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. The current experiments examined whether selective breeding for high alcohol preference in P rats may be associated with increased sensitivity of the posterior ventral tegmental area to the reinforcing properties of nicotine. P rats self-infused nicotine at lower concentrations as well received more nicotine infusions than Wistar rats. In addition, a 5HT3 receptor antagonist with nicotine reduced responding on the active lever. The data supports an association between selective breeding for high alcohol preference and increased sensitivity of the pVTA to the reinforcing properties of nicotine.

Original languageEnglish (US)
Pages (from-to)800-811
Number of pages12
JournalAddiction Biology
Volume19
Issue number5
DOIs
StatePublished - Sep 2014

Keywords

  • Alcohol-preferring rats
  • intracranial self-administration
  • nicotine self-infusions
  • serotonin-3 receptors
  • ventral tegmental area

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Psychiatry and Mental health
  • Pharmacology
  • Medicine(all)

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