Received for publication August 22, 2006.
Revised February 22, 2007.
Accepted for publication February 22, 2007.

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

Abstract

Rationale: 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 co-administration of a 5-HT₃ receptor antagonist. Objectives: 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. Methods: 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. Additionally, experiments examined the effects of co-infusion of the 5-HT₃ antagonist ICS 205,930 (ICS), and the DA D_2,3 agonist quinpirole on the self-infusion of CPBG. Results: 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). Co-infusion of either ICS or quinpirole reduced CPBG self-infusion into the posterior VTA. Conclusions: 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. Additionally, the data suggest that selective breeding for alcohol-preference results in the posterior VTA being more sensitive to the reinforcing effects of CPBG.

Key words: alcohol-preferring (P) rats, reinforcement, reward, self-administration, serotonin-3 receptors, ventral tegemental area