sb-242084 and 1-phenyl-3-dimethylamino-1-2-3-4-tetrahydronaphthalene

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.

Topics: Alcohol Drinking; Aminopyridines; Animals; Female; Indoles; Male; Rats; Rats, Sprague-Dawley; Receptors, Serotonin, 5-HT2; Reinforcement, Psychology; Serotonin 5-HT2 Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists; Tetrahydronaphthalenes