The reinforcing actions of a serotonin-3 receptor agonist within the ventral tegmental area: Evidence for subregional and genetic differences and involvement of dopamine neurons

Zachary A. Rodd, Victoria E. Gryszowka, Jamie E. Toalston, Scott M. Oster, Dong Ji, Richard L. Bell, William J. McBride

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Abstract

Studies from our laboratory indicated that local perfusion of the ventral tegmental area (VTA) with a serotonin-3 (5-HT3) receptor agonist increased dopamine (DA) neuronal activity and that the self-infusion of ethanol (EtOH) and cocaine into the posterior VTA could be inhibited with coadministration of a 5-HT3 receptor antagonist. The study tested the hypothesis that activating 5-HT3 receptors within the VTA produces reinforcing effects. The study also examined whether there were differences between Wistar rats and a line of rats selectively bred for high alcohol consumption with regard to the self-infusion of a 5-HT3 receptor agonist within the VTA. Adult female alcohol-preferring (P) and Wistar rats were allowed to self-infuse the 5-HT3 receptor agonist 1-(m-chlorophenyl)-biguanide (CPBG) into the posterior or anterior VTA. Furthermore, experiments examined the effects of coinfusion of the 5-HT 3 antagonist ICS 205,930 (ICS), and the DA D2,3 agonist quinpirole on the self-infusion of CPBG. Both Wistar and P rats readily self-administered CPBG into the posterior, but not anterior, VTA. P rats self-infused lower concentrations of CPBG (0.10 μM) than did Wistar rats (1.0 μM). Coinfusion of either ICS or quinpirole reduced CPBG self-infusion into the posterior VTA. The results of this study suggest that activation of 5-HT3 receptors within the posterior VTA produces reinforcing effects and that these reinforcing effects are mediated through activation of DA neurons. Furthermore, the data suggest that selective breeding for alcoholpreference results in the posterior VTA being more sensitive to the reinforcing effects of CPBG.

Original languageEnglish (US)
Pages (from-to)1003-1012
Number of pages10
JournalJournal of Pharmacology and Experimental Therapeutics
Volume321
Issue number3
DOIs
StatePublished - Jun 1 2007

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ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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