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-phenyl-dihydropyridinium (MPP+) tox icity 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 prob e in the striatum of freely moving mature C57BL/6 mice. The 60-min perfusio n of 10 and 100 muM 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 i ncreased the glutamate level at 100 muM, but not at 10 muM. The addition of 100 muM (+)-MK-801 or 200 muM (+/-)-AP-7 to the perfusate did not attenuat e MPP+-induced dopamine overflow. The extent of dopamine release only depen ded on the amount of MPP+ accumulation into the cells. These results indica ted that, at least in the striatum, neither glutamate release nor the NMDA antagonist, including (+)-MK-801, could regulate MPP+-evoked dopamine overf low.