Effects of antipsychotic drugs on latent inhibition: sensitivity and specificity of an animal behavioral model of clinical drug action.
Latent inhibition (LI) of a conditioned emotional response (CER) has been proposed as a quantitative measure of selective attention. We have assessed the parallels of the pharmacology of LI in rats with the clinical pharmacology of schizophrenia. Drug and vehicle treated rats were divided into groups and preexposed 20 times to cage illumination as a CS, or not preexposed. All groups were conditioned with 2 CS-footshock pairings. The following day CER, as measured by interruption of drinking 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 mg/kg enhanced LI, while doses of 0.003 and 3.0 mg/kg had no effect. Haloperidol enhancement of LI was unaffected by the coadministration of the anticholinergic agent trihexyphenidyl. Enhancement of LI is exhibited by the antipsychotic drugs fluphenazine, chlorpromazine, thiothixene, thioridazine, mesoridazine, and metoclopramide but not clozapine. The non-antipsychotic drugs pentobarbital, imipramine, chlordiazepoxide, trihexyphenidyl, and promethazine failed to enhance LI. LI exhibits striking parallels to the clinical pharmacology of schizophrenia.
Dunn
L A
LA
Department of Psychiatry, Duke University Medical Center, Durham, NC 27710.
Atwater
G E
GE
Kilts
C D
CD
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D018680:Cholinergic Antagonists / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004644:Emotions / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014282:Trihexyphenidyl / Q000494:pharmacology
D014150:Antipsychotic Agents; D018680:Cholinergic Antagonists; D014282:Trihexyphenidyl; D006220:Haloperidol