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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.

Authors

M.J. O'Callaghan

C. Bay-Richter

Colm M.P. O’ Tuathaigh

DAVID HEERY david.heery@nottingham.ac.uk
Professor of Eucaryoticgene Regulation

J.L. Waddington

DR PAULA MORAN paula.moran@nottingham.ac.uk
Associate Professor & Reader in Behavioural Neuroscience



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 http://eprints.nottingham.ac.uk/id/eprint/52889
Publisher URL http://journals.sagepub.com/doi/10.1177/0269881114544774
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





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