Irreversible suppression of alcohol drinking in cyanamide-treated rats after sustained delivery of the 5-HT2 antagonist amperozide.

The purpose of this study was to evaluate the long-term effect of sustained treatment with amperozide, which has been shown to attenuate the volitional drinking of ethyl alcohol in the rat without side effects. Preference for alcohol first was induced pharmacologically in Sprague-Dawley rats by the inhibitor of aldehyde dehydrogenase, cyanamide, administered in a dose of 10 mg/kg twice daily for 3 days. Then following a standard preference test, each rat was offered water and its maximally preferred concentration of alcohol which ranged from 7% to 15%. Following a 4-day pre-drug test, saline control vehicle or amperozide was administered for 7 days by an osmotic minipump implanted in the intrascapular space. A single dose of 208 micrograms/kg/h (i.e., 5.0 mg/kg/day) was selected on the basis of a prior dose response study of amperozide. During the interval of sustained release of amperozide, the consumption of alcohol declined significantly in terms of both absolute g/kg intake and proportion of alcohol to water. When the preference of the rats was retested at 4, 30, 70, 110, and 140 day intervals after the pump had exhausted amperozide, the absolute g/kg consumption of alcohol continued to decline significantly. Unlike other drugs, amperozide did not produce any side effects, particularly on the intake of food or water or on body weight, which suggests a pharmacological specificity of its action.(ABSTRACT TRUNCATED AT 250 WORDS)