SUPPRESSION BY MEMANTINE AND AMANTADINE OF SYNAPTIC EXCITATION INTRASTRIATALLY EVOKED IN RAT NEOSTRIATAL SLICES

The competitive N-methyl-D-aspartate (NMDA) receptor antagonists, DL-( E)-2-amino-4-methyl-5-phosphono-3-pentanoic acid (CGP 37849) and D(-)- 2-amino-5-phosphonovaleric acid (APV), and the non-competitive NMDA an tagonists, memantine and amantadine, which are used in the treatment o f Parkinson's disease, were tested for their effects on intrastriatall y evoked excitatory postsynaptic potentials (EPSPs) in rat neostriatal slices. Fast, non-NMDA receptor mediated synaptic excitation was not affected by any of the NMDA receptor antagonists. The NMDA component o f the EPSPs was more prominent following reduction of the non-NMDA com ponent of the EPSP by the non-NMDA receptor antagonist 6-cyano-7-nitro quinoxaline-2,3-dione (CNQX, 5-10 mu M). Memantine (30 mu M) and amant adine (100 mu M) had similar effects in reducing the NMDA component, b ut were not as effective as CCP 37849 (1-5 mu M) or APV (10 mu M). The data are compatible with a possible locus of action of memantine and amantadine in the neostriatum.