| Possible GABAergic mechanism in the neuroprotective effect of gabapentin and lamotrigine against 3-nitropropionic acid induced neurotoxicity. | |
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MedLine Citation:
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PMID: 22154757 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Huntington's disease is a progressive neurodegenerative disorder that gradually reduces memory, cognitive skills and normal movements of affected individuals. Systemic administration of 3-Nitropropionic acid induces selective striatal lesions in rodents and non-human primates. Therefore, the present study has been designed to elucidate the comparative mechanistic profile of gabapentin, lamotrigine and their interactions with GABAergic modulators against 3-Nitropropionic acid induced neurotoxicity. Systemic 3-Nitropropionic acid (10mg/kg) administration for 14days significantly reduced body weight, locomotor activity, grip strength, oxidative defense (LPO, nitrite, SOD and catalase) and impaired mitochondrial complex enzyme (I, II, IV and MTT assay) activities in the striatum. 3-Nitropropionic acid treatment also increased TNF-α level in the striatum. Gabapentin (50 and 100mg/kg) and lamotrigine (10, 20 and 40mg/kg) treatments significantly restored behavioural, oxidative defense and mitochondrial complex enzyme activities and proinflammatory markers (TNF-α) as compared to 3-Nitropropionic acid treated group. Systemic picrotoxin (1mg/kg) pretreatment with sub effective dose of gabapentin (50mg/kg) or lamotrigine (20mg/kg) significantly attenuated their protective effect. Further, GABA (50mg/kg) and/or muscimol (0.05mg/kg) pretreatment with sub effective dose gabapentin (50mg/kg) and lamotrigine (20mg/kg) significantly potentiated their protective effects which were significant as compared to their effect alone. The results of the present study suggest that a GABAergic mechanism is involved in the protective effect of gabapentin and lamotrigine against 3-Nitropropionic acid induced neurotoxicity. |
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Authors:
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Puneet Kumar; Harikesh Kalonia; Anil Kumar |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-28 |
Journal Detail:
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Title: European journal of pharmacology Volume: - ISSN: 1879-0712 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-12-13 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011. Published by Elsevier B.V. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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