SEROTONIN(3) RECEPTOR ANTAGONISM OF ALCOHOL INTAKE - EFFECTS OF DRINKING CONDITIONS

The effects of 5-HT3 receptor antagonists on ethanol intake were exami ned in the selectively bred alcohol-preferring P line of rats under co ntinuous and limited access to 10% (v/v) ethanol with food and water a d lib. Single daily injections of either MDL 72222 (MDL) or ICS 205-93 0 (ICS) (0.01-3.0 mg/kg, SC) given 60 min before a 4-h scheduled acces s period for 4 consecutive days failed at all doses to alter the intak e of a 10% (v/v) ethanol solution by P rats. However, multiple daily i njections of either MDL (1-3 mg/kg, SC) or ICS (3.0 and 5.0 mg/kg, SC) , given three times daily at 4-h intervals, significantly reduced etha nol intake under 24-h free-choice conditions on the first treatment da y. Additionally, a single administration of 1.0 mg/kg MDL reduced 24-h free-choice ethanol intake by approximately 50% of control values and had no effect on 24-h saccharin intake. The effects of MDL were furth er examined in a 2 h schedule access paradigm in which rats received t he access period at the same time every day (Fixed) or randomly during the dark cycle (Variable). Although 1.0 mg/kg MDL had little effect o n ethanol drinking in the Fixed group, ethanol intake was reduced by 5 5% of control levels in the Variable group. Overall, the data indicate that drinking conditions influence the effectiveness of 5-HT3 antagon ists to reduce ethanol consumption. Furthermore, the results suggest t hat conditions, associated with limited access ethanol drinking, marke dly reduce the actions of 5-HT3 antagonists on ethanol intake. (C) 199 8 Elsevier Science Inc.