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?
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 ant...
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| Format: | Article |
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Sage
2014
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| Online Access: | https://eprints.nottingham.ac.uk/52889/ |
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| author | O'Callaghan, M.J. Bay-Richter, C. O’ Tuathaigh, Colm M.P. Heery, David M. Waddington, J.L. Moran, Paula M. |
| author_facet | O'Callaghan, M.J. Bay-Richter, C. O’ Tuathaigh, Colm M.P. Heery, David M. Waddington, J.L. Moran, Paula M. |
| author_sort | O'Callaghan, M.J. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T20:26:03Z |
| format | Article |
| id | nottingham-52889 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T20:26:03Z |
| publishDate | 2014 |
| publisher | Sage |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-528892020-05-04T16:53:03Z https://eprints.nottingham.ac.uk/52889/ 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. 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. Sage 2014-10-01 Article PeerReviewed O'Callaghan, M.J., Bay-Richter, C., O’ Tuathaigh, Colm M.P., Heery, David M., Waddington, J.L. and Moran, Paula 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). pp. 973-977. ISSN 1461-7285 Antipsychotics; Drd-2 knockout mice; Latent inhibition; Haloperidol; Clozapine http://journals.sagepub.com/doi/10.1177/0269881114544774 doi:10.1177/0269881114544774 doi:10.1177/0269881114544774 |
| spellingShingle | Antipsychotics; Drd-2 knockout mice; Latent inhibition; Haloperidol; Clozapine O'Callaghan, M.J. Bay-Richter, C. O’ Tuathaigh, Colm M.P. Heery, David M. Waddington, J.L. Moran, Paula M. 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? |
| title | 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? |
| title_full | 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? |
| title_fullStr | 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? |
| title_full_unstemmed | 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? |
| title_short | 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? |
| title_sort | 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? |
| topic | Antipsychotics; Drd-2 knockout mice; Latent inhibition; Haloperidol; Clozapine |
| url | https://eprints.nottingham.ac.uk/52889/ https://eprints.nottingham.ac.uk/52889/ https://eprints.nottingham.ac.uk/52889/ |