Dopamine and glutamate control each other's release in the basal ganglia: a microdialysis study of the entopeduncular nucleus and substantia nigra.

This study utilized microdialysis in conscious rats to investigate dopaminergic control of excitatory amino acid release in the entopeduncular nucleus (EPN), and glutamatergic control of dopamine release in the substantia nigra pars reticulata (SNr). EPN dialysates contained both glutamate and aspartate, which were elevated by dopamine depletion with reserpine and 6-hydroxydopamine (6-OHDA), reduced by the D2/3 agonist LY 171555 and unaffected by the D1 agonist SKF 38393, in line with current theory. The D2/3 agonist RU 24213 was behaviourally active but paradoxically increased glutamate and aspartate release in EPN, possibly via kappa opioid receptor blockade. 6-OHDA-hemilesioned rats also showed a significant increase in glutamate and aspartate contralaterally, suggesting that nigrostriatal dopamine affects EPN neurotransmission bilaterally. In reserpine-treated rats, basal levels of dopamine in the SNr were greatly reduced, and were further lowered by focal application of NMDA antagonists, suggestive of the removal of a high glutamatergic tone. A threshold amount of L-DOPA applied to the SNr elevated dopamine output about two-fold and 5-HT output about 13-fold, indicating L-DOPA effects the release of monoamines other than dopamine. Concomitant addition of the NMDA antagonists potentiated these releases synergistically, suggesting that this could be how they facilitate the antiparkinsonian action of L-DOPA.