EVIDENCE FOR A STRIATAL NMDA RECEPTOR MODULATION OF NIGRAL GLUTAMATE RELEASE - A DUAL PROBE MICRODIALYSIS STUDY IN THE AWAKE FREELY MOVING RAT

Dual probe microdialysis was employed to characterize dialysate glutam ate levels from the substantia nigra pars reticulata of awake freely m oving rats, and to test its sensitivity to alterations in striatal neu rotransmission including striatal N-methyl-D-aspartic acid (NMDA) rece ptor stimulation and blockade. Intranigral perfusion with low (0.1 mM) Ca2+ medium (60 min) did not affect nigral glutamate levels, whereas intranigral perfusion with tetrodotoxin (10 mu M, 60 min) increased ni gral glutamate levels. Perfusion of KCl (100 mM, 10 min) in the dorsol ateral striatum transiently stimulated nigral glutamate levels (maxima l increase + 60%), whereas intrastriatal perfusion (60 min) with low C a2+ medium and tetrodotoxin gradually increased nigral glutamate level s. Intrastriatal perfusion with NMDA (0.1-100 mu M, 10 min) dose-depen dently stimulated glutamate levels in the substantia nigra pars reticu lata. The NMDA (1 mu M)-induced increase in nigral glutamate release w as transient and maximal (+60% within 20 min), whereas that for NMDA ( 10 mu M) had a slow onset but was long lasting (+35% after 60 min). Lo wer (0.1 mu M) and higher (100 mu M) NMDA concentrations were ineffect ive. The effect of intrastriatal NMDA (1 mu M) was prevented by coperf usion with MK-801 (1 mu M). Intrastriatal MK-801 (10 mu M) alone gradu ally increased glutamate levels up to +50% after 60 min of perfusion. The present results suggest that glutamate levels in the substantia ni gra pars reticulata are sensitive to changes in neuronal transmission in the dorsolateral striatum, and that striatal NMDA receptors regulat e nigral glutamate release in both a tonic and phasic fashion.