Effect of single and repeated methamphetamine treatment on neurotransmitter release in substantia nigra and neostriatum of the rat

The main purpose of this study was to characterize the initial neurotransmission cascade elicited by methamphetamine, analysing simultaneously with in vivo microdialysis monoamine, amino acid and neuropeptide release in substantia nigra and neostriatum of the rat. The main effect of a single systemic dose of methamphetamine (15 mg/kg, subcutaneously) was an increase in dopamine levels, both in substantia nigra (approximate to 10-fold) and neostriatum (approximate to 40-fold), accompanied by a significant, but lesser, increase in dynorphin B (approximate to two-fold, in both regions), and a decrease in monoamine metabolites. A similar effect was also observed after local administration of methamphetamine (100 mum) via the microdialysis probes, but restricted to the treated region. In other experiments, rats were repeatedly treated with methamphetamine or saline, with the last dose administered 12 h before microdialysis. Dopamine K+ -stimulated release was decreased following repeated methamphetamine administration compared with that following saline, both in the substantia nigra (by approximate to 65%) and neostriatum (by approximate to 20%). In contrast, the effect of K+ -depolarization on glutamate, aspartate and GABA levels was increased following repeated administration of methamphetamine. In conclusion, apart from an impairment of monoamine neurotransmission, repeated methamphetamine produces changes in amino acid homeostasis, probably leading to NMDA-receptor overstimulation.