Determination of extracellular glutamate after local K+ stimulation in the striatum of non-anaesthetised 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 pre-column 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+, 4mM 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 micrograms/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).
Institute for Pharmacology and Toxicology, Faculty of Pharmacy, University of Marburg, Federal Republic of Germany.
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Dietze
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Kuschinsky
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003956:Dialysis; D015259:Dopamine Agents / Q000494:pharmacology*; D004873:Ergolines / Q000494:pharmacology; D005971:Glutamates / Q000032:analysis / Q000378:metabolism*; D018698:Glutamic Acid; D008297:Male; D011188:Potassium / Q000494:pharmacology*; D019257:Quinpirole; D051381:Rats; D017208:Rats, Wistar; D013050:Spectrometry, Fluorescence; D013268:Stimulation, Chemical; D013469:Sulpiride / Q000494:pharmacology
D001381:Azepines; D015259:Dopamine Agents; D004873:Ergolines; D005971:Glutamates; D019257:Quinpirole; D018698:Glutamic Acid; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C024763:talipexole; D013469:Sulpiride; D001058:Apomorphine; D011188:Potassium