Disruption and potentiation of latent inhibition by risperidone: The latent inhibition model of atypicalantipsychotic action

Ina Weiner, Daniela Schiller, Inna Gaisler-Salomon

Research output: Contribution to journalArticlepeer-review

Abstract

Latent Inhibition (LI), that is, retarded conditioning to a Stimulus following its nonreinforced pre-exposure, is impaired in some subsets of schizophrenia patients and in amphetamine-treated rats. Potentiation of LI by antipsychotic drugs (APDs) given in conditioning, underconditions that do not lead to LI in controls, is a well-established index of antipsychotic activity. Recently, we have shown that the atypicalAPD, clozapine, in addition disrupts LI if administered in pre-exposure, under conditions that lead to LI in controls. This studydemonstrates the same behavioralprofilefortheatypicalAPDrisperidone. LI was measured in a thirst-motivated conditioned emotionalresponse procedure by comparing suppression of drinking in response to atone previously paired with afoot shock in rats that receivednonreinforced exposure to the tone priorto conditioning (pre-exposed (PE)) and rats for whom the tone was novel(non-pre-exposed(NPE)). We show that under conditions that did not yield LI in vehicle controls (40 pre-exposures and five conditioning trials), risperidone (0.25, 0.5, and 1.2 mg/kg) led to LI when administered in conditioning. Under conditions that led to LI in vehicle controls (40pre-exposures and two conditioning trials), risperidone (0.25, 0.5, and 2.5 mg/kg) abolished LI when administered in pre-exposure; thelatter effect was not evident with haloperidol. In addition, the effects of risperidone administered in both the pre-exposure andconditioning stages were dose-dependent so that the pre-exposure-based action was manifested at lower but not at higher doses. It isconcluded that atypicalAPDs exert in the LI modeladualpattern of effects, which enables detection of their ‘typical' action(conditioning-based LI potentiation) as wellasa dissociation from typicalAPDs by their ‘atypical' action (pre-exposure-based LIdisruption). It is suggested that the former and latter effects are subserved by D2 and 5HT2A antagonism, respectively.

Original languageEnglish
Pages (from-to)499-509
Number of pages11
JournalNeuropsychopharmacology
Volume28
Issue number3
DOIs
StatePublished - Mar 2003
Externally publishedYes

Keywords

  • Atypicalantipsychotic drugs
  • Haloperidol
  • Latent inhibition
  • Rat
  • Risperidone
  • Schizophrenia

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Pharmacology

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