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Effect of single and repeated methamphetamine treatment on neurotransmitter release in substantia nigra and neostriatum of the rat
Author(s) -
Bustamante Diego,
You ZhiBing,
Castel MarieNoëlle,
Johansson Sara,
Goiny Michel,
Terenius Lars,
Hökfelt Tomas,
HerreraMarschitz Mario
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2002.01171.x
Subject(s) - methamphetamine , microdialysis , substantia nigra , dopamine , monoamine neurotransmitter , neurotransmitter , chemistry , medicine , endocrinology , glutamate receptor , nmda receptor , homovanillic acid , catecholamine , pharmacology , biology , dopaminergic , central nervous system , receptor , serotonin
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 (≈ 10‐fold) and neostriatum (≈ 40‐fold), accompanied by a significant, but lesser, increase in dynorphin B (≈ two‐fold, in both regions), and a decrease in monoamine metabolites. A similar effect was also observed after local administration of methamphetamine (100 µ m ) 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 ≈ 65%) and neostriatum (by ≈ 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.