The latent inhibition model of schizophrenia: further validation using the atypical neuroleptic, clozapine

Biol Psychiatry. 1996 Nov 1;40(9):834-43. doi: 10.1016/0006-3223(95)00573-0.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antipsychotic Agents / therapeutic use*
  • Association Learning / drug effects
  • Attention / drug effects
  • Clozapine / therapeutic use*
  • Conditioning, Classical / drug effects*
  • Dextroamphetamine / pharmacology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Humans
  • Inhibition, Psychological*
  • Male
  • Mental Recall / drug effects
  • Rats
  • Rats, Wistar
  • Schizophrenia / diagnosis
  • Schizophrenia / drug therapy*
  • Schizophrenic Psychology*

Substances

  • Antipsychotic Agents
  • Clozapine
  • Dextroamphetamine