Serotonin3 Receptor Antagonism of Alcohol Intake: Effects of Drinking Conditions

McKINZIE, D. L., R. EHA, R. COX, R. B. STEWART, W. DYR, J. M. MURPHY, W. J. McBRIDE, L. LUMENGAND T.-K. LI. Serotonin₃ receptor antagonism of alcohol intake: Effects of drinking conditions. ALCOHOL 15(4) 291–298, 1998.—The effects of 5-HT₃ receptor antagonists on ethanol intake were examined in the selectively bred alcohol-preferring P line of rats under continuous and limited access to 10% (v/v) ethanol with food and water ad lib. Single daily injections of either MDL 72222 (MDL) or ICS 205-930 (ICS) (0.01–3.0 mg/kg, SC) given 60 min before a 4-h scheduled access period for 4 consecutive days failed at all doses to alter the intake of a 10% (v/v) ethanol solution by P rats. However, multiple daily injections 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 ethanol intake under 24-h free-choice conditions on the first treatment day. 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 further examined in a 2-h schedule access paradigm in which rats received the 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 on ethanol drinking in the Fixed group, ethanol intake was reduced by 55% of control levels in the Variable group. Overall, the data indicate that drinking conditions influence the effectiveness of 5-HT₃ antagonists to reduce ethanol consumption. Furthermore, the results suggest that conditions, associated with limited access ethanol drinking, markedly reduce the actions of 5-HT₃ antagonists on ethanol intake.