EFFECT OF COADMINISTRATION OF GLUTAMATE-RECEPTOR ANTAGONISTS AND DOPAMINERGIC AGONISTS ON LOCOMOTION IN MONOAMINE-DEPLETED RATS

Combinations of dopaminergic agonists with glutamate receptor antagoni sts have been suggested to be a possible alternative treatment of Park inson's disease. To gain further insights into this possibility, the a ntagonist of the competitive AMPA-type glutamate receptor NBQX and the ion-channel blocker of the NMDA glutamate receptor (+)-MK-801 in comb ination with the dopamine D1 receptor agonists: SKF 38393, SKF 82958, and dihydrexidine; the dopamine D2 receptor agonist bromocriptine and the dopamine-precursor L-DOPA were tested in rats pretreated with rese rpine and a-methyl-p-tyrosine. MK-801 on its own induced locomotor beh aviour and potentiated the antiakinetic effects of dihydrexidine and L -DOPA but not of the other dopamine agonists tested. NBQX neither on i ts own nor coadministered with the dopamine agonists tested had an ant iakinetic effect. These results indicate that agents, blocking the ion -channel of the NMDA receptor, might be useful adjuvants to some but n ot all dopaminomimetics in therapy of Parkinson's disease. The same do es not seem to be true for the AMPA-antagonist NBQX.