Yes / Background: Asenapine is a new pharmacological agent for the acute treatment of schizophrenia and bipolar disorder. It has relatively higher affinity for serotonergic and α2-adrenergic than dopaminergic D2 receptors. We evaluated the effects of asenapine, risperidone, and olanzapine on acute and subchronic psychotomimetic-induced disruption of cued reversal learning in rats.
Methods: After operant training, rats were treated acutely with D-amphetamine (0.75 mg/kg intraperitoneally [i.p.]) or phencyclidine (PCP; 1.5 mg/kg i.p.) or sub-chronically with PCP (2 mg/kg i.p. for 7 days). We assessed the effects of acute coadministration of asenapine, risperidone, or olanzapine on acute D-amphetamine– and PCP-induced deficits and the effects of long-term coadministration of these agents (for 28 additional days) on the deficits induced by subchronic PCP.
Results: Deficits in reversal learning induced by acute D-amphetamine were attenuated by risperidone (0.2 mg/kg i.p.). Acute PCP-induced impairment of reversal learning was attenuated by acute asenapine (0.025 mg/kg subcutaneously [s.c.]), risperidone (0.2 mg/kg i.p.), and olanzapine (1.0 mg/kg i.p.). Subchronic PCP administration induced an enduring deficit that was attenuated by acute asenapine (0.075 mg/kg s.c.) and by olanzapine (1.5 mg/kg i.p.). Asenapine (0.075 mg/kg s.c.), risperidone (0.2 mg/kg i.p.), and olanzapine (1.0 mg/kg i.p.) all showed sustained efficacy with chronic (29 d) treatment to improve subchronic PCP-induced impairments.
Conclusion: These data suggest that asenapine may have beneficial effects in the treatment of cognitive symptoms in schizophrenia. However, this remains to be validated by further clinical evaluation. / This research was supported by Schering-Plough Corporation, now Merck & Co., Inc. and Pfizer Inc.
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/8465 |
| Date | 31 May 2010 |
| Creators | McLean, Samantha, Neill, Joanna C., Idris, Nagi F., Marston, H.M., Wong, E.H.F., Shahid, M. |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Article, Accepted manuscript |
| Rights | © 2010 Elsevier B.V. Reproduced in accordance with the publisher's self-archiving policy. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/, CC-BY-NC-ND |
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