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Metabotropic glutamate receptor‐mediated inhibition and excitation of substantia nigra dopamine neurons
Author(s) -
Meltzer Leonard T.,
Serpa Kevin A.,
Christoffersen Curt L.
Publication year - 1997
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/(sici)1098-2396(199706)26:2<184::aid-syn9>3.0.co;2-4
Subject(s) - nbqx , ampa receptor , chemistry , metabotropic receptor , substantia nigra , acpd , bicuculline , metabotropic glutamate receptor , excitatory postsynaptic potential , neuroscience , inhibitory postsynaptic potential , pharmacology , agonist , glutamate receptor , dopaminergic , dopamine , antagonist , biology , biochemistry , receptor
Microiontophoretic drug application and extracellular recording techniques were used to evaluate the effects of the selective metabotropic glutamate receptor (mGluR) agonist (1S,3R)‐1‐aminocyclopentane‐1,3‐dicarboxylate (1S,3R‐ACPD) on dopamine (DA) neurons in the substantia nigra zona compacta (SNZC) of chloral hydrateanesthetized rats. 1S,3R‐ACPD had a biphasic effect on the firing rate of DA cells, initially decreasing, then increasing the firing rate. 1S,3R‐ACPD also increased the burst‐firing activity of DA neurons. Application of the ionotropic receptor (iGluR) agonists (R,S)‐α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA) or N‐methyl‐D‐aspartate (NMDA) increased the firing rates of neurons which had responded to 1S,3R‐ACPD, indicating that mGluRs and iGluRs reside on the same neurons. The initial inhibitory period was not antagonized by systemic haloperidol or iontophoretic bicuculline, indicating a lack of DA or γ‐amino‐n‐butyric acid (GABA) involvement in this effect. Combined application of the AMPA or γ‐amino‐n‐butyric acid (GABA) involvement in this effect. Combined application of the AMPA antagonist, 2,3‐dihydroxy‐6‐nitro‐7‐sulfamoyl‐benzo(f)quinoxaline (NBQX), and the NMDA antagonist, (I)‐3‐(2‐carboxypiperazin‐4‐yl)propyl‐1‐phosphoric acid (CPP), at currents which antagonized AMPA and NMDA, did not antagonize either the inhibitory or excitatory effects of 1S,3R‐ACPD. Application of the metabotropic antagonist (S)‐4‐carboxy‐phenylglycine antagonized both the inhibitory and excitatory effects of 1S‐3R‐ACPD. These results indicate that mGluRs may play a role in the modulation of dopaminergic activity in the SNZC. Synapse 26:184–193, 1997. © 1997 Wiley‐Liss, Inc.