Enhancement of avoidance-suppressing effect after repeated administration of haloperidol and serum haloperidol in rats.

Adult male rats of the Wistar strain, which were trained under a discriminated lever-press avoidance schedule (intertrial interval; 25 sec. presentation of conditioned stimuli; 5 sec), were given SC 0.025-0.05 mg/kg of haloperidol at fixed intervals of 1, 3-4 and 7 days. The avoidance-suppressing effect of haloperidol was enhanced in parallel to the number of drug administrations until it attained a maximum level. The intensity of the maximum effect tended to be stronger, and the number of administrations necessary to attain it was smaller, when a higher dose was given. When the administration interval exceeded one day, the enhanced effect remained irreversible one month after withdrawal of drug administration. The enhancement of the effect was produced after repeated administrations in an experimental chamber, but not in a home cage. Temporal changes in serum haloperidol concentration were determined 30-90 min after 0.035 mg/kg given SC to the haloperidol-pretreated and saline-pretreated groups. No significant difference in the pharmacokinetic change was detected between the two groups. These results suggest that learning during the drug effect under repeated exposure to a fixed experimental situation influences the enhancing effect.