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University Laboratory of Physiology, Oxford, UK.

1. Glutamate in the extracellular compartment of the striatum of freely moving rats was monitored at 5 min intervals using microdialysis and an enzyme-based assay. 2. Basal levels of dialysate glutamate were 3.6 +/- 0.5 microM. Local infusion through the dialysis probe of tetrodotoxin (TTX), cadmium chloride or magnesium chloride produced no reduction in basal levels of glutamate; with the latter two there was, instead, an increase. 3. Neuronal activation stimulated by induced grooming was accompanied by an increase in total glutamate efflux of 47.5 +/- 25.0% above basal level; this increase was not reduced by local infusion of TTX. 4. We propose that the TTX-insensitive release of glutamate in response to physiological stimulation is derived from glial cells and is a Ca(2+)-dependent mechanism triggered by a receptor-mediated release of Ca2+ from internal stores that spreads through the network of astrocytes.