DETERMINATION OF EXTRACELLULAR GLUTAMATE AFTER LOCAL K+ STIMULATION IN THE STRIATUM OF NONANAESTHETIZED RATS AFTER TREATMENT WITH DOPAMINERGIC DRUGS - STUDIES USING MICRODIALYSIS

The present experiments were performed in order to investigate the effects of dopamine(DA)ergic drugs on the concentrations of extracellular glutamate (GLU) in the striatum of non-anaesthetised, freely moving rats by using microdialysis and to get further information about the interactions between glutamatergic and dopaminergic pathways. GLU was determined after precolumn derivatisation with o-phthaldialdehyde by HPLC and fluorescence detection. For increasing the fraction of extracellular GLU which is of neuronal origin, an enhanced release of this neurotransmitter was evoked by 100 mM K+ administered via the dialysis probe. This stimulation was applied twice in each experiment, at the second time after administration of a subcutaneously (s.c.) given DAergic drug. For basal conditions, a perfusion fluid containing 148.2 mM Na+, 4 mM K+, 1.2 mM Ca2+ was used, for conditions of stimulation with 100 mM K+ the Na+ concentration was reduced correspondingly. Activation of the D1 receptor with the selective D1 sector agonist SKF 38393 ((+/-)1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol) 15 mg/kg) failed to influence the stimulated release of GLU, and neither a combination of the selective D2 antagonist (-) sulpiride (150 mg/kg) with the mixed D1/D2 agonist apomorphine (1 mg/kg), nor a combination of sulpiride (150 mg/kg) with SKF 38393 (15 mg/kg) were effective. Also the two selective D2 agonists quinpirole (0.5 mg/kg) or talipexole (50 mug/kg) had no significant influence on the release of GLU. The results suggest that DA receptor agonists have less effect on the K+-stimulated GLU-release than might be expected from in vitro studies or behavioral experiments (Kornhuber and Kornhuber, 1986).