Potentiation of Latent Inhibition by Haloperidol and Clozapine is Attenuated in Dopamine D2 Receptor (Drd-2)-deficient Mice: Do Antipsychotics Influence Learning to Ignore Irrelevant Stimuli Via Both Drd-2 and Non-Drd-2 Mechanisms?

Overview

Journal J Psychopharmacol

Publisher Sage Publications

Specialty Pharmacology

Date 2014 Aug 15

PMID 25122042

Citations 2

Authors

Matthew J OCallaghan

Cecilie Bay-Richter

Colm Mp OTuathaigh

David M Heery

John L Waddington

Paula M Moran

Affiliations

Soon will be listed here.

Abstract

Whether the dopamine Drd-2 receptor is necessary for the behavioural action of antipsychotic drugs is an important question, as Drd-2 antagonism is responsible for their debilitating motor side effects. Using Drd-2 null mice (Drd2 -/-) it has previously been shown that Drd-2 is not necessary for antipsychotic drugs to reverse D-amphetamine disruption of latent inhibition (LI), a behavioural measure of learning to ignore irrelevant stimuli. Weiner's 'two-headed' model indicates that antipsychotics not only reverse LI disruption, 'disrupted LI', but also potentiate LI when low/absent in controls, 'persistent' LI. We investigated whether antipsychotic drugs haloperidol or clozapine potentiated LI in wild-type controls or Drd2 -/-. Both drugs potentiated LI in wild-type but not in Drd2 -/- mice, suggesting moderation of this effect of antipsychotics in the absence of Drd-2. Haloperidol potentiated LI similarly in both Drd1 -/- and wild-type mice, indicating no such moderation in Drd1 -/-. These data suggest that antipsychotic drugs can have either Drd-2 or non-Drd-2 effects on learning to ignore irrelevant stimuli, depending on how the abnormality is produced. Identification of the non-Drd-2 mechanism may help to identify novel non-Drd2 based therapeutic strategies for psychosis.

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