PT  - JOURNAL ARTICLE
AU  - Zachary A. Rodd
AU  - Victoria E. Gryszowka
AU  - Jamie E. Toalston
AU  - Scott M. Oster
AU  - Dong Ji
AU  - Richard L. Bell
AU  - William J. McBride
TI  - 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
AID  - 10.1124/jpet.106.112607
DP  - 2007 Jun 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1003--1012
VI  - 321
IP  - 3
4099  - http://jpet.aspetjournals.org/content/321/3/1003.short
4100  - http://jpet.aspetjournals.org/content/321/3/1003.full
SO  - J Pharmacol Exp Ther2007 Jun 01; 321
AB  - 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 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 alcohol-preference results in the posterior VTA being more sensitive to the reinforcing effects of CPBG. The American Society for Pharmacology and Experimental Therapeutics