Abstract
: The present study was undertaken to investigate whether the relatively selective neuronal nitric oxide synthase (NOS) inhibitor, 7‐nitroindazole (7‐NI), protects against methamphetamine (METH)‐induced neurotoxicity. Male Swiss Webster mice received the following treatments (i.p.; q 3 h × 3): (a) vehicle/saline, (b) 7‐NI (25 mg/kg)/saline, (c) vehicle/METH (5 mg/kg), and (d) 7‐NI (25 mg/kg)/METH (5 mg/kg). On the second day, groups (a) and (b) received two vehicle injections, and groups (c) and (d) received two 7‐NI injections (25 mg/kg, each). Administration of vehicle/METH resulted in 68, 44, and 55% decreases in the concentration of dopamine, 3,4‐dihydroxyphenylacetic acid, and homovanillic acid, respectively, and a 48% decrease in the number of [3H]mazindol binding sites in the striatum compared with control values. Treatment with 7‐NI (group d) provided full protection against the depletion of dopamine and its metabolites and the loss of dopamine transporter binding sites. Administration of 7‐NI/saline (group b) affected neither the tissue concentration of dopamine and its metabolites nor the binding parameters of [3H]mazindol compared with control values. 7‐NI had no significant effect on animals' body temperature, and it did not affect METH‐induced hyperthermia. These findings indicate a role for nitric oxide in methamphetamine‐induced neurotoxicity and also suggest that blockade of NOS may be beneficial for the management of Parkinson's disease.
