Comparison of the efficacy of two anticonvulsants, phenytoin and valproate to improve PCP and d-amphetamine induced deficits in a reversal learning task in the rat
Recent studies in our laboratory have shown that PCP (phencyclidine) and d-amphetamine induce a cognitive deficit in rats, in a paradigm of potential relevance for the pathology of schizophrenia. Atypical, but not classical antipsychotics and the anticonvulsant, lamotrigine have been shown to preven...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2009-06-01
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| Series: | Frontiers in Behavioral Neuroscience |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/neuro.08.008.2009/full |
| _version_ | 1811257464554782720 |
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| author | Nagi F Idris JO C Neill Charles H Large |
| author_facet | Nagi F Idris JO C Neill Charles H Large |
| author_sort | Nagi F Idris |
| collection | DOAJ |
| description | Recent studies in our laboratory have shown that PCP (phencyclidine) and d-amphetamine induce a cognitive deficit in rats, in a paradigm of potential relevance for the pathology of schizophrenia. Atypical, but not classical antipsychotics and the anticonvulsant, lamotrigine have been shown to prevent a selective reversal learning deficit induced by PCP. In contrast, only haloperidol reversed the d-amphetamine-induced deficit. The present study aimed to explore the ability of two anticonvulsants with differing mechanism of action, valproate and phenytoin to attenuate the cognitive deficits induced by PCP and d-amphetamine in the reversal learning paradigm. PCP at 1.5mg/kg and d-amphetamine at 0.5mg/kg both produced a selective and significant reduction in performance of the reversal phase with no effect on the initial phase of the task in female-hooded Lister rats. Valproate (25-200mg/kg) and phenytoin (25-50mg/kg) had no effect on performance when administered alone. Valproate (100-200mg/kg), whose principle action is thought to be the enhancement of GABA transmission, was unable to prevent the cognitive deficit induced by either PCP or d-amphetamine. Conversely, phenytoin (50mg/kg), a use-dependent sodium channel inhibitor, significantly prevented the deficit induced by PCP, but not d-amphetamine. These results add to our earlier work with lamotrigine, and suggest that sodium channel blockade may be a mechanism by which some anticonvulsant drugs can prevent the PCP-induced deficit. These data have implications for the use of anticonvulsant drugs in the treatment of cognitive or psychotic disorders. |
| first_indexed | 2024-04-12T17:57:44Z |
| format | Article |
| id | doaj.art-cbb1b654c2104dbbadce1f46a66c474f |
| institution | Directory Open Access Journal |
| issn | 1662-5153 |
| language | English |
| last_indexed | 2024-04-12T17:57:44Z |
| publishDate | 2009-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Behavioral Neuroscience |
| spelling | doaj.art-cbb1b654c2104dbbadce1f46a66c474f2022-12-22T03:22:18ZengFrontiers Media S.A.Frontiers in Behavioral Neuroscience1662-51532009-06-01310.3389/neuro.08.008.2009551Comparison of the efficacy of two anticonvulsants, phenytoin and valproate to improve PCP and d-amphetamine induced deficits in a reversal learning task in the ratNagi F Idris0JO C Neill1Charles H Large2The University of BradfordThe University of BradfordGlaxosmithkline S.p.ARecent studies in our laboratory have shown that PCP (phencyclidine) and d-amphetamine induce a cognitive deficit in rats, in a paradigm of potential relevance for the pathology of schizophrenia. Atypical, but not classical antipsychotics and the anticonvulsant, lamotrigine have been shown to prevent a selective reversal learning deficit induced by PCP. In contrast, only haloperidol reversed the d-amphetamine-induced deficit. The present study aimed to explore the ability of two anticonvulsants with differing mechanism of action, valproate and phenytoin to attenuate the cognitive deficits induced by PCP and d-amphetamine in the reversal learning paradigm. PCP at 1.5mg/kg and d-amphetamine at 0.5mg/kg both produced a selective and significant reduction in performance of the reversal phase with no effect on the initial phase of the task in female-hooded Lister rats. Valproate (25-200mg/kg) and phenytoin (25-50mg/kg) had no effect on performance when administered alone. Valproate (100-200mg/kg), whose principle action is thought to be the enhancement of GABA transmission, was unable to prevent the cognitive deficit induced by either PCP or d-amphetamine. Conversely, phenytoin (50mg/kg), a use-dependent sodium channel inhibitor, significantly prevented the deficit induced by PCP, but not d-amphetamine. These results add to our earlier work with lamotrigine, and suggest that sodium channel blockade may be a mechanism by which some anticonvulsant drugs can prevent the PCP-induced deficit. These data have implications for the use of anticonvulsant drugs in the treatment of cognitive or psychotic disorders.http://journal.frontiersin.org/Journal/10.3389/neuro.08.008.2009/fullCognitionPhencyclidinePhenytoinReversal LearningSchizophreniarat |
| spellingShingle | Nagi F Idris JO C Neill Charles H Large Comparison of the efficacy of two anticonvulsants, phenytoin and valproate to improve PCP and d-amphetamine induced deficits in a reversal learning task in the rat Frontiers in Behavioral Neuroscience Cognition Phencyclidine Phenytoin Reversal Learning Schizophrenia rat |
| title | Comparison of the efficacy of two anticonvulsants, phenytoin and valproate to improve PCP and d-amphetamine induced deficits in a reversal learning task in the rat |
| title_full | Comparison of the efficacy of two anticonvulsants, phenytoin and valproate to improve PCP and d-amphetamine induced deficits in a reversal learning task in the rat |
| title_fullStr | Comparison of the efficacy of two anticonvulsants, phenytoin and valproate to improve PCP and d-amphetamine induced deficits in a reversal learning task in the rat |
| title_full_unstemmed | Comparison of the efficacy of two anticonvulsants, phenytoin and valproate to improve PCP and d-amphetamine induced deficits in a reversal learning task in the rat |
| title_short | Comparison of the efficacy of two anticonvulsants, phenytoin and valproate to improve PCP and d-amphetamine induced deficits in a reversal learning task in the rat |
| title_sort | comparison of the efficacy of two anticonvulsants phenytoin and valproate to improve pcp and d amphetamine induced deficits in a reversal learning task in the rat |
| topic | Cognition Phencyclidine Phenytoin Reversal Learning Schizophrenia rat |
| url | http://journal.frontiersin.org/Journal/10.3389/neuro.08.008.2009/full |
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