Effects of amperozide on schedule-induced polydipsia in rats

Abstract

Schedule-induced polydipsia occurs when food-deprived rats are exposed to a fixed-interval feeding schedule (FI = 60 s) for 1 h every day. Amperozide, a novel antipsychotic drug with a strong affinity for the 5-HT 2 receptor, was injected i.p. after completion of the requisite training sessions. The experimental rationale is that although the intensity of licking behavior in schedule-induced polydipsia can be taken as an index for anxiety, the drug-induced motor dysfunction should be assessed. In experiment 1, we tested the effect of amperozide on schedule-induced polydipsia at doses of 2, 4, and 8 mg/kg. The data showed that each dose significantly diminished the amount of licking and water intake. The number of presses decreased only at the dose of 8 mg/kg. During five post-treatment daily sessions for 5 days, these three measures returned to normal levels except that the number of pellets earned during the sessions did not significantly change. In addition, the number of presses showed a rebound after the termination of amperozide administration. In experiment 2, in addition to the total water intake, number of licks, pellets earned and presses, we also analyzed the postpellet temporal variation in the number of licks and presses in each schedule-induced polydipsia session. The drug was stopped for one day after each dose of 0.2, 0.4, 0.8 and 1.6 mg/kg of amperozide. The data showed that doses from 0.2 to 0.8 mg/kg did not alter any measure in drug-treated sessions and that the dose of 1.6 mg/kg decreased the number of licks and water intake. Taken together, these data suggest that, at the dose of 1.6–2.0 mg/kg, amperozide can reduce anxiety without causing motor dysfunction.