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dc.contributor.authorIdris, Nagi F.*
dc.contributor.authorRepeto, P.*
dc.contributor.authorNeill, Joanna C.*
dc.contributor.authorLarge, C.H.*
dc.date.accessioned2009-12-10T15:49:13Z
dc.date.available2009-12-10T15:49:13Z
dc.date.issued2005
dc.identifier.citationIdris, N. F., Repeto, P., Neill, J. C. and Large, C. H. (2005). Investigation of the effects of lamotrigine and clozapine in improving reversal-learning impairments induced by acute phencyclidine and D-amphetamine in the rat. Psychopharmacology, Vol. 179, No. 2, pp.336-348.en
dc.identifier.urihttp://hdl.handle.net/10454/4046
dc.descriptionnoen
dc.description.abstractRationale Phencyclidine (PCP), a glutamate/N-methyl-d-aspartate (NMDA) receptor antagonist, has been shown to induce a range of symptoms similar to those of patients with schizophrenia, while d-amphetamine induces predominantly positive symptoms. Previous studies in our laboratory have shown that PCP can selectively impair the performance of an operant reversal-learning task in the rat. Furthermore, we found that the novel antipsychotic ziprasidone, but not the classical antipsychotic haloperidol, could prevent the PCP-induced deficit. Objectives The aim of the present study was to validate the model further using the atypical antipsychotic clozapine and then to investigate the effects of lamotrigine, a broad-spectrum anticonvulsant that is known to reduce glutamate release in vitro and is able to prevent ketamine-induced psychotic symptoms in healthy human volunteers. A further aim was to compare effects of PCP and d-amphetamine in the test and investigate the effects of the typical antipsychotic haloperidol against the latter. Methods Female hooded-Lister rats were food deprived and trained to respond for food in a reversal-learning paradigm. Results PCP at 1.5 mg/kg and 2.0 mg/kg and d-amphetamine at 0.5 mg/kg significantly and selectively impaired performance in the reversal phase of the task. The cognitive deficit induced by 1.5 mg/kg PCP was attenuated by prior administration of lamotrigine (20 mg/kg and 30 mg/kg) or clozapine (5 mg/kg), but not haloperidol (0.05 mg/kg). In direct contrast, haloperidol (0.05 mg/kg), but not lamotrigine (25 mg/kg) or clozapine (5 mg/kg), prevented a similar cognitive impairment produced by d-amphetamine (0.5 mg/kg). Conclusions Our findings provide further data to support the use of PCP-induced disruption of reversal learning in rodents to investigate novel antipsychotic drugs. The results also provide evidence for different mechanisms of PCP and d-amphetamine-induced disruption of performance in the test, and their different sensitivities to typical and atypical antipsychotic drugs.en
dc.language.isoenen
dc.publisherSpringer Berlin / Heidelbergen
dc.relation.isreferencedbyhttp://dx.doi.org/10.1007/s00213-004-2058-5en
dc.subjectPhencyclidineen
dc.subjectd-Amphetamineen
dc.subjectReversal learningen
dc.subjectCognitive deficiten
dc.subjectSchizophreniaen
dc.subjectLamotrigineen
dc.subjectClozapineen
dc.subjectHaloperidolen
dc.subjectAntipsychoticsen
dc.titleInvestigation of the effects of lamotrigine and clozapine in improving reversal-learning impairments induced by acute phencyclidine and D-amphetamine in the rat.en
dc.status.refereedYesen
dc.typeArticleen
dc.type.versionpublished version paperen


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