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Eur J Pharmacol. 2013 Oct 15;718(1-3):98-104. doi: 10.1016/j.ejphar.2013.09.008. Epub 2013 Sep 13.

The serotonin-2 receptor modulator, (-)-trans-PAT, decreases voluntary ethanol consumption in rats.

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  • 1University of Florida, Department of Pharmacodynamics, Box 100487, 1600 SW Archer Road, Gainesville, FL 32610, USA.

Abstract

Serotonin (5-HT) 5-HT2C receptor agonists have shown promise as novel alcoholism pharmacotherapies, but developing selective agonists has been problematic. Female Sprague Dawley rats were given ethanol in a palatable gel vehicle during operant sessions. 5-HT2C receptor modulators (Ro60-0175, SB242,084, and (-)-trans-PAT) were administered before operant sessions. As a control for the effects of 5-HT2C receptor agonism on caloric intake, drugs were also tested using non-ethanol containing gelatin. Ro60-0175, a 5-HT2 family receptor agonist, decreased both ethanol and vehicle responding while (-)-trans-PAT, a 5-HT2C receptor agonist with 5-HT2A-2B receptor inverse agonist activity, selectively reduced only ethanol responding. The effect of 5-HT2C receptor agonists on self-administration after reinstatement of ethanol after a three week deprivation was also determined. (-)-trans-PAT eliminated increases in ethanol intake following ethanol deprivation whereas Ro60-0175 had no effect. These results emphasize the need for caloric controls and further support the idea that selective modulation of 5-HT2 family receptors is a potential pharmacotherapeutic approach in the treatment of alcoholism.

© 2013 Elsevier B.V. All rights reserved.

KEYWORDS:

Alcohol deprivation; Alcoholism; Ethanol; Operant self-administration; Serotonin 2C receptor

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