Document Detail

Possible GABAergic mechanism in the neuroprotective effect of gabapentin and lamotrigine against 3-nitropropionic acid induced neurotoxicity.
MedLine Citation:
PMID:  22154757     Owner:  NLM     Status:  MEDLINE    
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 (10 mg/kg) administration for 14 days 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 100 mg/kg) and lamotrigine (10, 20 and 40 mg/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 (1 mg/kg) pretreatment with sub effective dose of gabapentin (50 mg/kg) or lamotrigine (20mg/kg) significantly attenuated their protective effect. Further, GABA (50 mg/kg) and/or muscimol (0.05 mg/kg) pretreatment with sub effective dose gabapentin (50 mg/kg) and lamotrigine (20 mg/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.
Puneet Kumar; Harikesh Kalonia; Anil Kumar
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Publication Detail:
Type:  Journal Article     Date:  2011-11-28
Journal Detail:
Title:  European journal of pharmacology     Volume:  674     ISSN:  1879-0712     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-01-09     Completed Date:  2012-05-03     Revised Date:  2013-08-21    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  265-74     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier B.V. All rights reserved.
Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre for Advanced Study, Panjab University, Chandigarh-160014, India.
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MeSH Terms
Amines / pharmacology*
Body Weight / drug effects
Brain / cytology,  drug effects,  enzymology,  metabolism
Catalase / metabolism
Cyclohexanecarboxylic Acids / pharmacology*
GABAergic Neurons / cytology,  drug effects*,  enzymology,  metabolism
Huntington Disease / pathology
Lipid Peroxidation / drug effects
Locomotion / drug effects
Mitochondria / drug effects,  enzymology
Neuroprotective Agents / pharmacology*
Neurotoxins / toxicity*
Nitrites / metabolism
Nitro Compounds / toxicity*
Oxidative Stress / drug effects
Propionates / toxicity*
Rats, Wistar
Rotarod Performance Test
Superoxide Dismutase / metabolism
Triazines / pharmacology*
Tumor Necrosis Factor-alpha / metabolism
gamma-Aminobutyric Acid / metabolism*,  pharmacology
Reg. No./Substance:
0/Amines; 0/Cyclohexanecarboxylic Acids; 0/Neuroprotective Agents; 0/Neurotoxins; 0/Nitrites; 0/Nitro Compounds; 0/Propionates; 0/Triazines; 0/Tumor Necrosis Factor-alpha; 504-88-1/3-nitropropionic acid; 56-12-2/gamma-Aminobutyric Acid; 6CW7F3G59X/gabapentin; EC; EC Dismutase; U3H27498KS/lamotrigine

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