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

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.

Citation

James Kasper, Rajiv Tikamdas, Myong Sang Kim, Kaley Macfadyen, Richard Aramini, Joseph Ladd, Sarah Bisceglia, Raymond Booth, Joanna Peris. The serotonin-2 receptor modulator, (-)-trans-PAT, decreases voluntary ethanol consumption in rats. European journal of pharmacology. 2013 Oct 15;718(1-3):98-104

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PMID: 24041931

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