BEHAVIORAL PHARMACOLOGY OF GLUTAMATE RECEPTORS IN THE BASAL GANGLIA

Glutamate receptors play a major role in the transmitter balance withi n the basal ganglia (BG). N-methyl-D-aspartate (NMDA) receptor stimula tion within the striatum acts behaviourally depressant while intrastri atal as well as systemic administration of NMDA receptor antagonists h ave rather stimulatory effects despite the different profiles of non-c ompetitive-, competitive NMDA receptor- and glycine site-antagonists. In animal models of Parkinson's disease all these NMDA receptor antago nists counteract parkinsonian symptoms or act synergistically with L-3 ,4-dihydroxyphenylalanine (L-DOPA). The strong locomotion-inducing eff ect of the non-competitive NMDA receptor antagonists is partly, but no t fully, mediated by a dopamine (DA) release in the nucleus accumbens. Manipulations at pha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate ( AMPA) receptors produce poor behavioural effects. These, however, are different or even opposed to NMDA receptor mediated effects. Local inf usions of AMPA receptor antagonists into the BG output nuclei have an antiparkinsonian effect but systemic injections are ineffective. These drugs even counteract the anti-parkinsonian effect of DA agonists and of non-competitive NMDA receptor antagonists as well as the DA releas ing effects of the latter drugs. Only few data on the role of metabotr opic receptors exist but the different receptor subtypes with differen t regional distribution represent a promising target for pharmacologic al interventions. (C) 1997 Elsevier Science Ltd.