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BEHAVIORAL PHARMACOLOGY

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

Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, Indiana (Z.A.R., V.E.G., D.J., R.L.B., W.J.M.), and Department of Psychology, Purdue School of Science, Indiana University-Purdue University at Indianapolis, Indianapolis, Indiana (J.E.T., S.M.O.).

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-HT₃ antagonist ICS 205,930 (ICS), and the DA D_2,3 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 alcohol-preference results in the posterior VTA being more sensitive to the reinforcing effects of CPBG.

Address correspondence to: Dr. Zachary A. Rodd, Indiana University School of Medicine, Institute of Psychiatric Research, 791 Union Drive, Indianapolis, IN 46202–4887. E-mail: zrodd{at}iupui.edu

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