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.
Colm M.P. O’ Tuathaigh
DAVID HEERY email@example.com
Professor of Eucaryoticgene Regulation
Paula M. Moran
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.
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|
|Peer Reviewed||Peer Reviewed|
|Keywords||Antipsychotics; Drd-2 knockout mice; Latent inhibition; Haloperidol; Clozapine|
|Copyright Statement||Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0|
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0
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