| Tiagabine, a GABA uptake inhibitor, attenuates 3-nitropropionic acid-induced alterations in various behavioral and biochemical parameters in rats. | |
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MedLine Citation:
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PMID: 18234412 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Huntington's disease is an incurable, adult-onset, dominantly inherited neurodegenerative disease. The clinical symptoms of the disease are primarily related to the progressive death of medium spiny gamma-amino butyric acid (GABAergic) neurons in the striatum and the deep layers of the cortex. Further in the later stage of life, the degeneration extends to a variety of brain regions, including the hypothalamus and hippocampus. Various GABAergic agents are being attempted for the treatment of Huntington's disease. Tiagabine [(R)-N-(4, 4-di-(3-methylthien-2-yl) but-3-enyl) nipecotic acid], a GABA uptake inhibitor, widely used in the treatment of seizures, is suggested to have neuroprotective properties. However, none of the study has elucidated its effect in the treatment of Huntington's disease and related pathologies. We explored whether tiagabine may attenuate various behavioral and biochemical alterations induced by systemic administration of 3-nitropropionic acid (an inhibitor of complex II of the electron transport chain), an accepted experimental animal model of Huntington's disease phenotype. Intraperitoneal administration of 3-nitropropionic acid (20 mg/kg., i.p.) for 4 days produced hypolocomotion, muscle incoordination and memory deficit. Daily treatment with tiagabine (5 and 10 mg/kg., i.p.) 30 min prior to 3-nitropropionic acid administration for a total of 4 days, significantly improved the 3-nitropropionic acid-induced motor and cognitive impairment. Biochemical analysis of the whole brain revealed that systemic 3-nitropropionic acid administration significantly increased lipid peroxidation, nitrite levels, total RNA levels and decreased reduced glutathione and succinate dehydrogenase activity which was reversed by daily treatment with tiagabine. Further, there was a decrease in adrenal ascorbic acid levels following daily administration of 3-nitropropionic acid, which was reversed by administration of tiagabine. The results of the present study indicate that tiagabine (5 and 10 mg/kg., i.p.) significantly reversed 3-nitropropionic acid-induced alterations in various behavioral and biochemical parameters and it could be a therapeutic agent for the treatment of Huntington's disease. |
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Authors:
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Ashish Dhir; Kiran Kumar Akula; S K Kulkarni |
Publication Detail:
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Type: Journal Article Date: 2008-01-29 |
Journal Detail:
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Title: Progress in neuro-psychopharmacology & biological psychiatry Volume: 32 ISSN: 0278-5846 ISO Abbreviation: Prog. Neuropsychopharmacol. Biol. Psychiatry Publication Date: 2008 Apr |
Date Detail:
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Created Date: 2008-03-05 Completed Date: 2008-07-02 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8211617 Medline TA: Prog Neuropsychopharmacol Biol Psychiatry Country: England |
Other Details:
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Languages: eng Pagination: 835-43 Citation Subset: IM |
Affiliation:
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Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh-160014, India. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Behavior, Animal / drug effects* Brain Chemistry / drug effects* Disease Models, Animal Dose-Response Relationship, Drug Drug Interactions GABA Agonists / therapeutic use* Glutathione / metabolism Huntington Disease / chemically induced, physiopathology, prevention & control* Lipid Peroxidation / drug effects Male Memory Disorders / etiology, prevention & control Motor Activity / drug effects Nipecotic Acids / therapeutic use* Nitro Compounds* Nitroprusside / metabolism Propionic Acids* RNA / metabolism Rats Rats, Wistar Rotarod Performance Test / methods |
| Chemical | |
Reg. No./Substance:
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0/GABA Agonists; 0/Nipecotic Acids; 0/Nitro Compounds; 0/Propionic Acids; 115103-54-3/tiagabine; 15078-28-1/Nitroprusside; 504-88-1/3-nitropropionic acid; 63231-63-0/RNA; 70-18-8/Glutathione |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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