Effect of low doses of L-NAME on methamphetamine-induced dopaminergic depletion in the rat striatum

The toxic dose of methamphetamine (METH) (5 mg/kg, s.c., x4, 2 hr intervals ) decreased contents of dopamine. dihydroxyphenylacetic acid (DOPAC), and h omovanillic acid (HVA) in striatum, and decreased contents of serotonin (5- HT) in both striatum and nucleus accumbens. Administration of low doses of a non-selective endothelial and neuronal nitric oxide synthase (NOS) inhibi tor, N omega -nitro-L-arginine methyl ester (L-NAME) (5 and 10 mg/kg, i.p., x 1) intensified the METH-induced decreases in contents of dopamine and it s metabolites in striatum. NO substrate, L-arginine (500 mg/kg, i.p., x4) r eversed these effects of L-NAME on the METH-neurotoxicity. L-NAME did not c hange the METH-induced hyperthermia. These findings, which are contrary to our previous study with a high dose of L-NAME, suggest that the inhibition of endothelial or neuronal NOS-mediated NO production by low doses of L-NAM E enhanced the METH-induced neurotoxicity. The finding that L-NAME can have opposite effects on the METH-neurotoxicity according to the dosing is impo rtant, however, additional experiments should be performed to clarify which type of NOS is related to these effects.