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.

Full Abstract

Studies from our laboratory indicated that local perfusion of the ventral tegmental area (VTA) with a serotonin-3 (5-HT(3)) 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-HT(3) receptor antagonist. The study tested the hypothesis that activating 5-HT(3) 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-HT(3) receptor agonist within the VTA. Adult female alcohol-preferring (P) and Wistar rats were allowed to self-infuse the 5-HT(3) 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 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 microM) than did Wistar rats (1.0 microM). Coinfusion of either ICS or quinpirole reduced CPBG self-infusion into the posterior VTA. The results of this study suggest that activation of 5-HT(3) 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.

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Author information

Author/s: Rodd, Zachary A (ZA); Gryszowka, Victoria E (VE); Toalston, Jamie E (JE); Oster, Scott M (SM); Ji, Dong (D); Bell, Richard L (RL); McBride, William J (WJ);

Affiliation: Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, 791 Union Drive, Indianapolis, IN 46202-4887, USA. zrodd(-atsign-)iupui.edu

Grants: AA07611 (Agency:NIAAA NIH HHS) ; AA10721 (Agency:NIAAA NIH HHS) ; AA11261 (Agency:NIAAA NIH HHS) ; AA12262 (Agency:NIAAA NIH HHS) ; R01 AA012262-06A2 (Agency:NIAAA NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther), published in United States. (Language: eng)

Reference: 2007-Jun; vol 321 (issue 3) : pp 1003-12

Dates: Created 2007/05/15; Completed 2007/07/30; Revised 2008/11/20;

PMID: 17325230, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Alcohol Drinking - genetics; psychology
Animals
Biguanides - administration & dosage; pharmacology
Cerebrospinal Fluid - chemistry
Conditioning, Classical - drug effects; physiology
Dopamine - metabolism
Dopamine Agonists - pharmacology
Female
Indoles - pharmacology
Infusions, Parenteral

Neurons - drug effects; metabolism; physiology
Quinpirole - pharmacology
Rats
Rats, Wistar
Receptors, Serotonin, 5-HT3 - agonists
Reinforcement (Psychology)
Self Administration - methods; psychology
Serotonin Agonists - administration & dosage; pharmacology
Serotonin Antagonists - pharmacology
Ventral Tegmental Area - drug effects; physiology

Associated Chemicals: Biguanides (0) ; Dopamine Agonists (0) ; Indoles (0) ; Receptors, Serotonin, 5-HT3 (0) ; Serotonin Agonists (0) ; Serotonin Antagonists (0) ; 1-(3-chlorophenyl)biguanide (48144-44-1) ; Dopamine (51-61-6) ; Quinpirole (85760-74-3) ; tropisetron (89565-68-4)

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