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-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.
Footnotes
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This work was supported in part by Research Grants AA10721, AA11261, and AA12262 and by Center Grant AA07611 from National Institute on Alcohol Abuse and Alcoholism.
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.106.112607.
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ABBREVIATIONS: 5-HT, serotonin, ICSA, intracranial self-administration; ICS 205,930 (ICS), tropisetron; CPBG, 1-(m-chlorophenyl)-biguanide; P rat, alcohol-preferring rat; EtOH, ethanol; aCSF, artificial cerebrospinal fluid; LY278-584, 1-methyl-N-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-1H-indazole-3-carboxamide; ANOVA, analysis of variance; DA, dopamine.
- Received August 17, 2006.
- Accepted February 22, 2007.
- The American Society for Pharmacology and Experimental Therapeutics
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