• Hokkaido Igaku Zasshi · Jan 1997

    [Experimental study of methamphetamine psychosis--role of glutamate and nitric oxide in methamphetamine-induced dopaminergic and serotonergic neurotoxicity in the rat brain].

    • T Abekawa.
    • Department of Psychiatry, Hokkaido University School of Medicine, Sapporo, Japan.
    • Hokkaido Igaku Zasshi. 1997 Jan 1; 72 (1): 113-26.

    AbstractThe present study examined effects of a high dose of methamphetamine (MA) (5mg/kg, s.c., x 4) on extracellular concentrations of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), 5-hydroxyindoleacetic acid (5-HIAA) and glutamate in rat striatum (ST) and nucleus accumbens (NA) using microdialysis. The toxic dose of MA markedly increased extracellular DA, and decreased DOPAC and 5-HIAA in both ST and NA. The increase in DA release was not different in magnitude between ST and NA. Extracellular glutamate showed a delayed increase in ST, but not in NA. Tissue contents of serotonin (5-HT) and 5-HIAA significantly decreased in both ST and NA, whereas those of DA, DOPAC and HVA decreased in ST but did not change in NA. These data suggest that the marked increase of DA release is not directly related to the MA-induced dopaminergic neurotoxicity. The increase in glutamate release found only in ST may be related to the dopaminergic damage in ST. However, enhancement in glutamate release did not appear to be essential for the serotonergic neurotoxicity. Nitric oxide (NO) has recently been recognized as a novel neuronal messenger. Taking into account the relationship between NMDA receptor activation and NO formation, the present study examined effects of a NO synthesis inhibitor, N omega-nitro-L-arginine methyl ester (LNAME) on MA-induced decreases in contents of the monoamines and their metabolites, in order to clarify whether the MA-induced dopaminergic and serotonergic neurotoxicity would be mediated by NO synthesis. Coadministration with LNAME (30 mg/kg, i.p., x2), reduced the MA-induced decreases in contents of DA, DOPAC and HVA in ST, but not reduced the MA-induced decreases in contents of 5-HT in ST and NA. These findings suggest that the MA-induced dopaminergic, but not serotonergic neurotoxicity, may be related to the neural process such as NO formation caused by the activation of postsynaptic DA receptor.

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