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 ( approximately 10-fold) and neostriatum ( approximately 40-fold), accompanied by a significant, but lesser, increase in dynorphin B ( approximately two-fold, in both regions), and a decrease in monoamine metabolites. A similar effect was also observed after local administration of methamphetamine (100 microm) 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 approximately 65%) and neostriatum (by approximately 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.
Bustamante
Diego
D
Programme of Molecular & Clinical Pharmacology, ICBM, Medical Faculty, University of Chile, Santiago 7, Casilla 70.000, Chile.
You
Zhi-Bing
ZB
Castel
Marie-Noëlle
MN
Johansson
Sara
S
Goiny
Michel
M
Terenius
Lars
L
Hökfelt
Tomas
T
Herrera-Marschitz
Mario
M
D000596:Amino Acids / Q000032:analysis / Q000378:metabolism; D000818:Animals; D001224:Aspartic Acid / Q000032:analysis / Q000378:metabolism; D015306:Biogenic Monoamines / Q000032:analysis / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004298:Dopamine / Q000032:analysis / Q000378:metabolism; D004333:Drug Administration Routes; D004334:Drug Administration Schedule; D004399:Dynorphins / Q000032:analysis / Q000378:metabolism; D004723:Endorphins / Q000032:analysis / Q000378:metabolism; D005110:Extracellular Space / Q000737:chemistry / Q000378:metabolism; D018698:Glutamic Acid / Q000032:analysis / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D017551:Microdialysis; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000032:analysis / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000032:analysis / Q000378:metabolism
D000596:Amino Acids; D015306:Biogenic Monoamines; D000697:Central Nervous System Stimulants; D004723:Endorphins; D018377:Neurotransmitter Agents; D001224:Aspartic Acid; D018698:Glutamic Acid; D008694:Methamphetamine; D005680:gamma-Aminobutyric Acid; D004399:Dynorphins; C036200:rimorphin; D011188:Potassium; D004298:Dopamine