title: Selective Nitric Oxide Synthase Inhibitor 7-Nitroindazole Protects against Cocaine-Induced Oxidative Stress in Rat Brain.
abstract: One of the mechanisms involved in the development of addiction, as well as in brain toxicity, is the oxidative stress. The aim of the current study was to investigate the effects of 7-nitroindazole (7-NI), a selective inhibitor of neuronal nitric oxide synthase (nNOS), on cocaine withdrawal and neurotoxicity in male Wistar rats. The animals were divided into four groups: control; group treated with cocaine (15 mg/kg(-1), i.p., 7 days); group treated with 7-NI (25 mg/kg(-1), i.p., 7 days); and a combination group (7-NI + cocaine). Cocaine repeated treatment resulted in development of physical dependence, judged by withdrawal symptoms (decreased locomotion, increased salivation and breathing rate), accompanied by an increased nNOS activity and oxidative stress. The latter was discerned by an increased formation of malondialdehyde (MDA), depletion of reduced glutathione (GSH) levels, and impairment of the enzymatic antioxidant defense system measured in whole brain. In synaptosomes, isolated from cocaine-treated rats, mitochondrial activity and GSH levels were also decreased. 7-NI administered along with cocaine not only attenuated the withdrawal, due to its nNOS inhibition, but also reversed both the GSH levels and antioxidant enzyme activities near control levels.
authors.affiliation: Laboratory of "Drug Metabolism and Drug Toxicity", Department of "Pharmacology, Pharmacotherapy and Toxicology", Faculty of Pharmacy, Medical University of Sofia, 2 "Dunav" Street, 1000 Sofia, Bulgaria.
authors.forename: Vessela
authors.initials: V
authors.lastname: Vitcheva
authors.affiliation: Laboratory of "Drug Metabolism and Drug Toxicity", Department of "Pharmacology, Pharmacotherapy and Toxicology", Faculty of Pharmacy, Medical University of Sofia, 2 "Dunav" Street, 1000 Sofia, Bulgaria.
authors.forename: Rumyana
authors.initials: R
authors.lastname: Simeonova
authors.affiliation: Laboratory of "Drug Metabolism and Drug Toxicity", Department of "Pharmacology, Pharmacotherapy and Toxicology", Faculty of Pharmacy, Medical University of Sofia, 2 "Dunav" Street, 1000 Sofia, Bulgaria.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kondeva-Burdina
authors.affiliation: Laboratory of "Drug Metabolism and Drug Toxicity", Department of "Pharmacology, Pharmacotherapy and Toxicology", Faculty of Pharmacy, Medical University of Sofia, 2 "Dunav" Street, 1000 Sofia, Bulgaria.
authors.forename: Mitka
authors.initials: M
authors.lastname: Mitcheva
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D003042:Cocaine / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007191:Indazoles / Q000494:pharmacology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism
chemical_list: D007191:Indazoles; D020011:Protective Agents; D008315:Malondialdehyde; D002374:Catalase; D005979:Glutathione Peroxidase; D052248:Nitric Oxide Synthase Type I; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D005978:Glutathione; D003042:Cocaine; C080122:7-nitroindazole