Conditioning and the delayed onset of a haloperidol-induced behavioral effect.

In a series of experiments, rats were given daily injections of 0.3 mg/kg haloperidol or vehicle 1 hr prior to behavioral testing. In these experiments, when rats were placed in an illuminated compartment and given the opportunity to enter a darkened compartment, haloperidol- and vehicle-treated rats initially entered the dark compartment with similar latencies. With repeated treatments, however, the haloperidol group gradually took increasingly longer times to enter the dark compartment. Furthermore, when the drug treatments of the groups were reversed, behavioral performance was dissociated from the drug state of the animal. Vehicle rats switched to haloperidol entered the dark compartment much more rapidly than haloperidol rats switched to vehicle. As additional control procedures, rats were given haloperidol 1 hr posttrial or were given haloperidol and only placed in the dark compartment. These haloperidol treatments did not differ from vehicle treatments. The gradual development of long latencies to initiate behavior and the persistence of this behavior during withdrawal from the haloperidol are consistent with the establishment of a conditioned drug response. This observation suggests that conditioning may contribute to the delayed onset of response in the clinical use of neuroleptic drugs.