Intermittent Retraining Attenuate Pimozide-Induced Avoidance Deficits

BENINGER, R. J., A. G. PHILLIPS AND H. C. FIBIGER. Prior training and intermittent retraining attenuate pimozide-induced avoidance deficits. PHARMACOL BIOCHEM BEHAV 18(4) 619--624, 1983.--Although the effects of neuroleptics on avoidance behavior have been studied extensively, no studies have systematically investigated the possible relationship between these effects and prior training. This paper reports the effects of prior training and intermittent retraining on pimozide-induced avoidance deficits. Experiment 1 investigated the effects of pimozide (0.5 or 1.0 mg/kg IP) on one-way avoidance responding in groups of rats (n= 15 or 16) that had received 0, 2, 3, or 10 prior sessions of training (10 trials per session). All trained groups were more resistant to the disruptive effects of the drug than the groups receiving no prior training but the 2, 3, and 10 session pretrained groups did not differ significantly from one another. However, the avoidance responding of the pretrained groups eventually was impaired across the 15 sessions of testing under the drug condition; this effect was shown not to be attributable to an accumulation of the drug with repeated dosing. Experiment 2 showed that periodic retraining in the absence of pimozide reversed the cumulative session-to-session disruptive effects of the low and high dose of pimozide on avoidance responding, a finding not previously reported. The results suggest that dopaminergic systems play a role in the acquisition and maintenance of operant response learning. Avoidance learning fails to occur if training is conducted in untrained, pimozide-treated animals. Pretrained animals, when injected with pimozide, can maintain avoidance responding for several sessions but lose this ability in the continued absence of normal dopamine function; however, intermittent retraining can prevent this eventual loss of avoidance responding.