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?

O'Callaghan, M.J.; Bay-Richter, C.; O� Tuathaigh, Colm M.P.; Heery, David M.; Waddington, J.L.; Moran, Paula M.

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.

Citation

O'Callaghan, M., Bay-Richter, C., O’ Tuathaigh, C. M., Heery, D. M., Waddington, J., & Moran, P. M. (2014). 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?. Journal of Psychopharmacology, 28(10), https://doi.org/10.1177/0269881114544774

• Journal Article Type: Article
• Acceptance Date: Dec 3, 2013
• Online Publication Date: Aug 13, 2014
• Publication Date: Oct 1, 2014
• Deposit Date: Jul 12, 2018
• Publicly Available Date: Jul 12, 2018
• Journal: Journal of Psychopharmacology
• Print ISSN: 0269-8811
• Electronic ISSN: 1461-7285
• Publisher: SAGE Publications
• Peer Reviewed: Peer Reviewed
• Volume: 28
• Issue: 10
• DOI: https://doi.org/10.1177/0269881114544774
• Keywords: Antipsychotics; Drd-2 knockout mice; Latent inhibition; Haloperidol; Clozapine
• Public URL: https://nottingham-repository.worktribe.com/output/734791
• Publisher URL: http://journals.sagepub.com/doi/10.1177/0269881114544774
• Contract Date: Jul 12, 2018