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• W2081016411 abstract "ABSTRACT: Methamphetamine (METH) is one of the major drugs of abuse that is postulated to cause neurotoxicity by depleting dopamine (DA) and its metabolites, high-affinity DA uptake sites, and the activity of tyrosine hydroxylase. The present study was undertaken to investigate whether the relatively selective, neuronal nitric oxide synthase (NOS) inhibitor, 7-nitroindazole (7-NI), protects against METH-induced neurotoxicity. Male Swiss Webster mice received the following injections intraperitoneally (i.p.) 3 times (every 3 hr): (i) vehicle/saline, (ii) 7-NI (25 mg/kg)/saline, (iii) vehicle/METH (5 mg/kg), and (iv) 7-NI (25 mg/kg)/METH (5 mg/kg). On the second day, groups (i) and (iii) received two vehicle injections and groups (ii) and (iv) received two 7-NI injections (25 mg/kg each). The administration of vehicle/METH resulted in 68, 44 and 55% decreases in the concentration of DA, dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA), respectively, and a 48% decrease in the number of [3H]mazindol binding sites in the striatum compared to control values. The treatment with 7-NI (group iv) provided a full protection against the depletion of DA and its metabolites, and the loss of dopamine transporter binding sites. Multiple injection of METH caused a significant decrease in the concentration of serotonin (5-HT) and its metabolite 5-hydroxyindole acetic acid (5-HIAA). Treatment with 7-NI partially blocked the depletion of 5-HT and completely blocked the reduction in 5-HIAA levels. The administration of 7-NI/saline (group ii) affected neither the tissue concentration of DA, 5-HT and their metabolites (DOPAC, HVA and 5-HIAA) nor the binding parameters of [3H]-mazindol compared to control (vehicle/saline) values. 7-NI had no significant effect on the animals' body temperature, and it did not affect METH-induced hyperthermia. These findings indicate a role for nitric oxide in METH-induced neurotoxicity and also suggest that blockage of NOS may be beneficial for the management of Parkinson's disease." @default.
• W2081016411 created "2016-06-24" @default.
• W2081016411 creator A5016755104 @default.
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• W2081016411 date "1998-05-01" @default.
• W2081016411 modified "2023-10-16" @default.
• W2081016411 title "Effects of 7-Nitroindazole, an NOS Inhibitor on Methamphetamine-Induced Dopaminergic and Serotonergic Neurotoxicity in Mice^a" @default.
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• W2081016411 doi "https://doi.org/10.1111/j.1749-6632.1998.tb08227.x" @default.
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