title: Protective role of sertraline against 3-nitropropionic acid-induced cognitive dysfunction and redox ratio in striatum, cortex and hippocampus of rat brain.
abstract: Huntington's disease (HD) is an inherited progressive neurodegenerative disorder in human characterized by progressive loss of movement and cognitive disturbances. 3-nitropropionic acid (3-NP; a mitochondrial toxin) produces age-dependent oxidative linked striatal damage, responsible for HD like symptoms. In the present study protective effect of sertraline in 3-NP induced HD like symptoms was evaluated in rats. Systemic administration of 3-NP (10 mg/kg for 14 days) resulted in impairment of memory as assessed in Morris water maze and elevated plus paradigm tasks. Biochemical analysis revealed that systemic 3-NP administration significantly impaired reduced glutathione, total glutathione, oxidized glutathione and glutathione-S-transferase levels, whereas the level of acetylcholinesterase enzyme increased in striatum, cortex and hippocampus regions of rat brain. Sertraline (5 and 10 mg/kg po) treatment once daily for 14 days significantly improved cognitive performance tasks and glutathione levels in 3-NP treated group. However, combination of yohimbine (2 mg/kg) (non selective serotonin receptors antagonist) with the higher dose of sertraline (10 mg/kg) did not influence the protective action of sertraline. Result shows that neuroprotective and antioxidant like effect of sertraline is independent of its conventional action on 5-HT receptor.
authors: Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
authors: Puneet
authors: P
authors: Kumar
authors: Anil
authors: A
authors: Kumar
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000633:toxicity; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects*; D003072:Cognition Disorders / Q000139:chemically induced / Q000517:prevention & control*; D003342:Corpus Striatum / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009498:Neurotoxins / Q000633:toxicity; D009574:Nitro Compounds / Q000633:toxicity*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D011422:Propionates / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D020280:Sertraline / Q000494:pharmacology*
chemical_list: D000928:Antidepressive Agents; D000959:Antihypertensive Agents; D009498:Neurotoxins; D009574:Nitro Compounds; D011422:Propionates; D000110:Acetylcholinesterase; D005978:Glutathione; D020280:Sertraline; C015392:3-nitropropionic acid