Operant conditioning and haloperidol-induced hypokinetic effects.

The present report presents evidence that operant conditioning processes may contribute to hypokinetic effects in rats induced by repeated haloperidol (HAL) treatments. Twenty-four male Sprague-Dawley rats were subdivided into three equal groups and given 9 daily injections of either 0.1 or 1.0 mg/kg HAL, i.p., or the lactic acid vehicle 1 h before testing of motoric behavior. The effects of the HAL were dependent upon dose and the test situation. In an open field, 1.0 HAL produced a complete akinesia whereas 0.1 HAL initially had no effect, but with repeated treatments the 0.1-HAL-treated rats became hypokinetic. When the animals were tested for their response to enter a dark compartment, the 2 doses had equivalent effects. Initially, HAL had no effect, but with repeated treatments, latencies to enter the dark compartment increased at the equivalent rates for the 0.1 and 1.0 HAL groups. When conditioned drug effects were assessed following withdrawal, only in drug environment situations which operant behavior occurred initially did hypokinesia persist. These results are relevant to understanding the delayed onset of action and antipsychotic effects of neuroleptic drugs.