N-methyl-D-aspartate receptors mediate a slow excitatory postsynaptic potential in the rat midbrain dopaminergic neurons.
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.
Mercuri
N B
NB
Clinica Neurologica Dip. Sanita' Pubblica, Universita' di Roma Tor Vergata, Italy.
Grillner
P
P
Bernardi
G
G
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D007649:Ketamine / Q000494:pharmacology; D008564:Membrane Potentials; D008636:Mesencephalon / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013378:Substantia Nigra / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013681:Tegmentum Mesencephali / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
D015763:2-Amino-5-phosphonovalerate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D001640:Bicuculline; D004298:Dopamine; D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine; D010852:Picrotoxin; D016194:Receptors, N-Methyl-D-Aspartate; D013779:Tetrodotoxin; C017069:bicuculline methiodide