Dopamine-glutamate interactions in methamphetaminc-induced neurotoxicity

Abstract

Repeated administration of methamphetamine (m-AMPH) to rats induces dopamine (DA) terminal damage, and coadministration of antagonists of the N-methyl-D-aspartate (NMDA) or dopamine D1 or D2 receptors are protective. Striatal microdialysis of rats given a neurotoxic regimen of 4 x m-AMPH (4 mg/kg, s.c.) treatments revealed a dramatic and prolonged elevation of extracellular DA after the final m-AMPH administration. Neuroprotective regimens of MK-801, SCH 23390, or eticlopride greatly attenuated the overflow of DA resulting from the fourth m-AMPH treatment. By itself, MK-801 had no significant influence on striatal DA overflow, whereas either DA antagonist given alone elevated dialysate DA concentrations. A significant correlation was found between the magnitude of the m-AMPH-induced DA overflow of individual microdialyzed rats and their striatal DA content at sacrifice one week later. We conclude that the ability of non-competitive NMDA antagonists and of the D1 or D2 antagonists to protect against m-AMPH-induced striatal DA terminal injury can be accounted for by their attenuation of m-AMPH-evoked DA overflow. These findings underscore the important role played by elevated extracellular DA concentrations to the injurious effects of this stimulant drug.

Disparity in the temporal appearance of methamphetamine-induced apoptosis and depletion of dopamine terminal markers in the striatum of mice

“…Thus, it is plausible to suspect that the striatal apoptosis induced by METH may be initiated by the excessive release of glutamate. Two pieces of evidence support this hypothesis, (1) METH induces the striatal overflow of glutamate as measured by in vivo microdialysis [23], and (2) antagonists of the NMDA receptor attenuate METH-induced DA terminal injury in the striatum [20,22,32].…”

Inhibition by dizocilpine (MK‐801) of striatal dopamine release induced by MPTP and MPP+: possible action at the dopamine transporter

“…The latter action could also be relevant to methamphetamine toxicity, which is inhibited by MK-801 by a mechanism that remains to be fully understood (Marshall et al, 1993). Since it appears that the massive methamphetamine-induced release of cytosolic dopamine plays a causal role in the subsequent degeneration of dopaminergic nerve terminals (Weihmuller et al, 1992;Marshall et al, 1993), it will be of interest to examine the possibility that MK-801 inhibits the dopamine transporter in vivo.…”

Methamphetamine-induced striatal apoptosis in the mouse brain: Comparison of a binge to an acute bolus drug administration

“…Thus, it is plausible to suspect that the striatal apoptosis induced by METH may be mediated by excessive release of glutamate. METH-induced overflow of glutamate in the striatum has been demonstrated (Nash and Yamamoto, 1992), and METH-induced dopamine terminal injury is prevented by NMDA receptor antagonists (Marshall et al, 1993;Muraki et al, 1992;Sonsalla et al, 1991).…”