Presynaptic Glutamate Receptors Modulate Dopamine Release from Striatal Synaptosomes

The wide‐ranging neuronal actions of glutamate arc thought to be mediated by postsynaptic N‐methyl‐D‐aspartate (NMDA) and non‐NMDA receptors. The present report demonstrates the existence of presynaptic glutamate receptors in isolated striatal dopaminergic nerve terminals (synaptosomes). Activation of these receptors, by NMDA in the absence of Mg2+ and presence of glycine and by non‐NMDA agonists in the presence of Mg2+, results in Ca2+‐depeodent release of dopamine from striatal synaptosomes. The release stimulated by NMDA is blocked by Mg2+ and by selective NMDA antagonists, whereas the release stimulated by selective non‐NMDA agonists is blocked by a non‐NMDA antagonist but not by Mg2+ or NMDA antagonists. Thus, these presynaptic glutamate receptors, localized on dopaminergic terminals in the striatum, appear to be pharmacologically similar to both the NMDA and the non‐NMDA postsynaptic receptors. By modulating the release of dopamine, these presynaptic receptors may play an important rote in transmitter interactions in die striatum.