EFFECTS OF ANTIPSYCHOTIC-DRUGS ON LATENT INHIBITION - SENSITIVITY ANDSPECIFICITY OF AN ANIMAL BEHAVIORAL-MODEL OF CLINICAL DRUG-ACTION

Latent inhibition (LI) of a conditioned emotional response (CER) has b een proposed as a quantitative measure of selective attention. We have assessed the parallels of the pharmacology of LI in rats with the cli nical pharmacology of schizophrenia. Drug and vehicle treated rats wer e divided into groups and preexposed 20 times to cage illumination as a CS, or not preexposed. All groups were conditioned with 2 CS-footsho ck pairings. The following day CER, as measured by interruption of dri nking in response to CS presentation, was recorded. LI was observed as a decreased CER in preexposed relative to non-preexposed animals. LI was enhanced by haloperidol 0.3 mg/kg after 7 or 14 daily treatments, but not after a single acute dose. Haloperidol doses of 0.3 and 0.03 m g/kg enhanced LI, while doses of 0.003 and 3.0 mg/kg had no effect. Ha loperidol enhancement of LI was unaffected by the coadministration of the anticholinergic agent trihexyphenidyl. Enhancement of LI is exhibi ted by the antipsychotic drugs fluphenazine, chlorpromazine, thiothixe ne, thioridazine, mesoridazine, and metoclopramide but not clozapine. The non-antipsychotic drugs pentobarbital, imipramine, chlordiazepoxid e, trihexyphenidyl, and promethazine failed to enhance LI. LI exhibits striking parallels to the clinical pharmacology of schizophrenia.