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

Serotonin (5 HT) 5-1-IT20 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 5-1-IT2 family receptor agonist, decreased both ethanol and vehicle responding while (-)-transPAT, 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 pharrnacotherapeutic approach in the treatment of alcoholism. (C) 2013 Elsevier EN. All rights reserved