The latent inhibition model of schizophrenia: further validation using the atypical neuroleptic, clozapine.
Latent inhibition (LI) refers to retarded conditioning to a stimulus that has been repeatedly presented without reinforcement. LI is impaired in schizophrenia patients and in rats treated with amphetamine. Neuroleptic drugs produce two effects in this test paradigm: antagonism of amphetamine-induced disruption of LI, and enhancement of LI when administered on their own. The present experiments tested the effects of the atypical neuroleptic, clozapine, on LI. The experiments used a conditioned emotional response procedure in rats licking for water, consisting of three stages: preexposure, in which the to-be-conditioned stimulus (tone) was repeatedly presented without reinforcement; conditioning, in which the preexposed stimulus was paired with reinforcement (foot shock); and test, in which LI was indexed by animals' degree of suppression of licking during tone presentation. In experiments 1 and 2, the effects of 5.0 and 10.0 mg/kg clozapine on LI were assessed following 20 or 10 tone preexposures, respectively. Experiments 3 and 4 used 40 preexposures and investigated antagonism of amphetamine-induced disruption of LI by 5.0 and 10.0 mg/kg clozapine, respectively. The results demonstrated that clozapine possesses a neuroleptic profile in the LI model, namely, it facilitates the development of LI and antagonizes amphetamine-induced disruption of LI.
Department of Psychology, Tel-Aviv University, Israel.
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Weiner
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Shadach
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Tarrasch
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Kidron
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Feldon
D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001245:Association Learning / Q000187:drug effects; D001288:Attention / Q000187:drug effects; D003024:Clozapine / Q000627:therapeutic use*; D003214:Conditioning, Classical / Q000187:drug effects*; D003913:Dextroamphetamine / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007266:Inhibition, Psychological; D008297:Male; D011939:Mental Recall / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology
D014150:Antipsychotic Agents; D003024:Clozapine; D003913:Dextroamphetamine