title: Prolonged pretreatment with carvedilol prevents 3-nitropropionic acid-induced behavioral alterations and oxidative stress in rats.
abstract: 3-nitropropionic acid (3-NP)-induced neurotoxicity causes a cellular energy deficit and oxidative stress via an irreversible inhibition of the mitochondrial enzyme succinate dehydrogenase (SDH). Systemic administration of 3-NP causes motor and cognitive deficits, particularly those associated with excessive free radical generation. Recently, carvedilol has been implicated as a neuroprotectant in the treatment of various neurological disorders. The present study was designed to investigate the neuroprotective effects of carvedilol against 3-NP-induced cognitive impairment and oxidative damage in rats. Intraperitoneal administration of 3-NP (20 mg/kg for 4 days) caused significant body weight reduction, impaired motor function (locomotor activity, movement pattern), induced vacuous chewing movements, led to poor retention of memory in the Morris water maze, and elevated plus maze task paradigms. Chronic treatment with carvedilol (1 and 2 mg/kg, po), once daily for a period of 8 days beginning 4 days before 3-NP administration, significantly reversed 3-NP-induced motor impairment and cognitive deficits. However, carvedilol (1 and 2 mg/kg, po) treatment significantly attenuated oxidative damage (reduced lipid peroxidation and nitrite levels, and restored depleted reduced glutathione and succinate dehydrogenase enzyme activity) in the rat brain. The results of the present study suggest that carvedilol has a neuroprotective effect against 3-NP-induced behavioral alterations and oxidative damage.
authors.affiliation: Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh-160014, India.
authors.forename: Puneet
authors.initials: P
authors.lastname: Kumar
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D003292:Convulsants / Q000494:pharmacology*; D005145:Face; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009055:Mouth; D009068:Movement / Q000187:drug effects; D009573:Nitrites / Q000378:metabolism; D009574:Nitro Compounds / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009949:Orientation / Q000187:drug effects; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D011412:Propanolamines / Q000494:pharmacology*; D011422:Propionates / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013385:Succinate Dehydrogenase / Q000378:metabolism
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D003292:Convulsants; D009573:Nitrites; D009574:Nitro Compounds; D011412:Propanolamines; D011422:Propionates; D000077261:Carvedilol; D013385:Succinate Dehydrogenase; D005978:Glutathione; C015392:3-nitropropionic acid