L-GLUTAMATE EXCITATION OF A10-DOPAMINE NEURONS IS PREFERENTIALLY MEDIATED BY ACTIVATION OF NMDA RECEPTORS - EXTRACELLULAR AND INTRACELLULARELECTROPHYSIOLOGICAL 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 neuro ns in rat midbrain slices using extracellular and intracellular record ing methods. L-Glutamate perfusion of 10-100 muM concentrations produc ed dose-dependent increases in firing rate, with no changes in pattern of firing, while higher concentrations led to a loss of activity remi niscent of depolarization inactivation. The extracellular changes were reflected by the pronounced membrane depolarizations observed through intracellular recordings. The effects of low doses (less-than-or-equa l-to 30 muM) Of L-GLU on firing rate and membrane potential were compl etely 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 > 300 muM L-GLU's effects could not be completely blocked without the presence of both CGS 19755 and NBQX. Moreover, th e magnitude Of L-GLU-induced depolarizations became attenuated at memb rane potentials more negative than -70 mV. These results suggest that in physiological-like conditions that low extracellular levels of glut amate excite midbrain dopamine neurons via a preferential activation o f NMDA receptors, and that only at higher concentrations of L-GLU are non-NMDA receptors brought into play.