ENHANCEMENT OF LATENT INHIBITION IN THE RAT BY THE CCK ANTAGONIST PROGLUMIDE

The behavioral paradigm of latent inhibition (LI) involves the retarda tion of conditioning to a stimulus when paired with reinforcement, if preexposure to that stimulus with no significant consequence has occur red. This phenomenon is believed to reflect a process of learning to i gnore stimuli as irrelevant. Disruption in LI can be considered to be an attentional deficit observed in schizophrenia. The neuropeptide cho lecystokinin (CCK), which coexists with dopamine (DA) in some brain re gions, has been implicated in the pathophysiology of schizophrenia. Th e present study examined the effects of the nonselective CCK antagonis t proglumide on LI (0.25, 0.5, and 1.0 mg/kg) using a conditioned supp ression of drinking procedure in rats. For purposes of comparison the effects of haloperidol (0.1 mg/kg) were also investigated. Administrat ion pf 1.0 and 0.5 mg/kg, but not 0.25 mg/kg, proglumide was found to reduce suppression of drinking behavior in animals preexposed (PE) to a flashing light stimulus. These animals developed LI under conditions where preexposed control animals exhibited suppression of drinking be havior similar to that of nonpreexposed (NPE) control animals. These f indings for proglumide were comparable to the effects on drinking beha vior of 0.1 mg/kg haloperidol. The enhancement of LI by proglumide may be interpreted in terms of CCK-dopamine interactions. Because CCK may modulate dopamine, the results reported here for proglumide strengthe n the argument for the investigation of CCK-based drugs as potential a ntipsychotic agents. (C) 1998 Elsevier Science Inc.