N-methyl-D-aspartate receptors mediate a slow excitatory postsynaptic potential in the rat midbrain dopaminergic...

Repetitive local application of a short train of stimuli to the rat substantia nigra and ventral tegmental area elicited a predominant depolarizing, slow, long-lasting synaptic response in the dopaminergic cells intracellularly recorded in vitro. This slow excitatory postsynaptic potential ranged between 13 and 27 mV at holding potentials of about-75 mV and lasted for 0.2-6 s. It was not greatly affected by the perfusion of 6-cyano-7-nitroquinoxaline-2,3-dione (10-20 microM), while it was potentiated in the presence of bicuculline methiodide (30 microM) or picrotoxin (50-100 microM) and 2-hydroxysaclofen (100-300 microM). In contrast, a substantial component of the slow excitatory postsynaptic potential was reversibly depressed, in a concentration-dependent manner, by the application of the N-methyl-D-aspartate receptor antagonists D,1-2-amino-5-phosphonovalerate (10-100 microM). Furthermore, the slow excitatory postsynaptic potential was reversibly increased by the superfusion of nominally magnesium-free solution. It was graded, increasing in amplitude with increased stimulus intensity, and was blocked by tetrodotoxin (0.5 microM). We suggest that a sustained activation of synaptic terminals containing excitatory amino acids mediates a slow excitatory postsynaptic potential in the dopaminergic cells of the midbrain. N-Methyl-D-aspartate receptors participate in the generation of this slow potential, while the alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionate/kainate receptors do not seem to contribute substantially to this potential. This N-methyl-D-aspartate-mediated synaptic event could be implicated in the release of dopamine as well as in the excitotoxic injury of the dopaminergic neurons.