Glutamate is not involved in the MPP+-induced dopamine overflow in the striatum of freely moving C57BL/6 mice.
The role of glutamate in the N-methyl-4-phenyldihydropyridinium (MPP+) toxicity has been argued in the past decade. However, the effects of glutamate efflux and NMDA antagonist on MPP+-induced dopamine overflow have not been documented. To clarify this, we perfused MPP+ through a microdialysis probe in the striatum of freely moving mature C57BL/6 mice. The 60-min perfusion of 10 and 100 microM MPP+ strikingly increased dopamine levels to 28- and 93-fold of the basal values, respectively. In contrast, an administration of MPP+ did not induce marked glutamate release: the MPP+-perfusion slightly increased the glutamate level at 100 microM, but not at 10 microM. The addition of 100 microM (+)-MK-801 or 200 microM (+/-)-AP-7 to the perfusate did not attenuate MPP+-induced dopamine overflow. The extent of dopamine release only depended on the amount of MPP+ accumulation into the cells. These results indicated that, at least in the striatum, neither glutamate release nor the NMDA antagonist, including (+)-MK-801, could regulate MPP+-evoked dopamine overflow.
Uezono
T
T
Department of Legal Medicine, Asahikawa Medical College, Japan.
Matsubara
K
K
Shimizu
K
K
Mizukami
H
H
Ogawa
K
K
Saito
O
O
Hayase
N
N
Eto
H
H
Kimura
K
K
Shiono
H
H
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006540:Herbicides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017551:Microdialysis; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D020734:Parkinsonian Disorders / Q000378:metabolism* / Q000503:physiopathology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D006540:Herbicides; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine