Failure of the 5-HT2 receptor antagonist, ritanserin, to alter preference for alcohol in drinking rats

The purpose of this study was to determine whether the 5-HT2 receptor antagonist, ritanserin, possesses the same sort of efficacy as another central 5-HT2 antagonist, amperozide, in reducing the pharmacologically induced preference for ethyl alcohol in the rat. Following the repeated administration of the inhibitor of aldehyde dehydrogenase, cyanamide, the preference for alcohol vs. water was determined in each of 20 Sprague-Dawley rats by a standard test using 3-30% concentrations. Then, each rat was offered water and its maximally preferred concentration of alcohol, which ranged from 9-15% and was consumed at a mean of 5.02 +/- 0.44 g/kg per day. After a 4-day predrug control test, either the saline control solution or 0.1, 0.3, or 1.0 mg/kg ritanserin was administered SC at 1600 h over 3 days. The daily intakes of alcohol of rats both during and after treatment with ritanserin were unchanged in terms of absolute g/kg and proportion of alcohol to total fluid consumed. Similarly, the control saline also was without any effect on alcohol consumption. Neither the consumption of food and total fluids nor the level of body weight was affected by these doses of ritanserin. Because our findings fail to coincide with previous reports on the effect of ritanserin on alcohol preference, it is envisaged that a methodological difference in earlier experimental procedures, such as the use of a weak 3% concentration of alcohol, could explain the discrepancy. Further, the present results contrast with the prolonged reduction in drinking produced by another 5-HT2 receptor antagonist, amperozide, which also acts centrally on dopaminergic neurons in the limbic system.