L-glutamate excitation of A10 dopamine neurons is preferentially mediated by activation of NMDA receptors: extra- and intracellular electrophysiological studies in brain slices.
The aim of the present study was to assess the effects of L-glutamate (L-GLU) on the neurophysiology of ventral tegmental A10 dopamine neurons in rat midbrain slices using extracellular and intracellular recording methods. L-Glutamate perfusion of 10-100 microM concentrations produced dose-dependent increases in firing rate, with no changes in pattern of firing, while higher concentrations led to a loss of activity reminiscent of depolarization inactivation. The extracellular changes were reflected by the pronounced membrane depolarizations observed through intracellular recordings. The effects of low doses (< or = 30 microM) of L-GLU on firing rate and membrane potential were completely antagonized by co-perfusion with the noncompetitive NMDA blocker, phencyclidine, or the selective competitive NMDA receptor antagonist, CGS 19755, but not by the selective non-NMDA blocker NBQX. However, at concentrations of > or = 300 microM L-GLU's effects could not be completely blocked without the presence of both CGS 19755 and NBQX. Moreover, the magnitude of L-GLU-induced depolarizations became attenuated at membrane potentials more negative than -70 mV. These results suggest that in physiological-like conditions that low extracellular levels of glutamate excite midbrain dopamine neurons via a preferential activation of NMDA receptors, and that only at higher concentrations of L-GLU are non-NMDA receptors brought into play.
Wang
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Department of Pharmacology, College of Medicine, University of Arizona, Tucson 85724.
French
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D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004298:Dopamine / Q000032:analysis*; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000737:chemistry / Q000187:drug effects*; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D017557:Ventral Tegmental Area / Q000187:drug effects*
D005971:Glutamates; D018377:Neurotransmitter Agents; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D004298:Dopamine