Evidence for N-methyl-D-aspartate and AMPA subtypes of the glutamate receptor on substantia nigra dopamine neurons: possible preferential role for N-methyl-D-aspartate receptors.

The present studies utilized extracellular single-unit recordings in chloral hydrate-anesthetized rats to evaluate the contribution of N-methyl-D-aspartate (NMDA) and (R,S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) subtypes of glutamate receptors to the excitatory effects of glutamate on substantia nigra dopamine neurons. Iontophoretic administration of NMDA, AMPA and glutamate increased the firing rate and amount of burst-firing of dopamine neurons. Iontophoretic application of the NMDA antagonist (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-l-phosphonic acid (CPP) inhibited the excitatory effect of NMDA and glutamate, but not that of AMPA. Iontophoretic application of the AMPA antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)-quinoxaline (NBQX), inhibited the excitatory effect of AMPA and glutamate, but not that of NMDA. CPP produced a greater antagonism of the glutamate excitation than did NBQX. In addition, CPP, but not NBQX, reduced the firing rate and burst-firing of a subpopulation of DA neurons. These data indicate that both NMDA and AMPA receptors are present on substantia nigra dopamine neurons and suggest that NMDA receptors may be more sensitive than AMPA receptors to endogenous glutamate and that a tonic glutamate tone, acting via NMDA receptor stimulation, may modulate the firing rate and burst-firing activity of some dopamine neurons.