ROLE OF D-1 RECEPTOR MECHANISMS IN THE POTENTIATION OF MOTOR-RESPONSES TO L-DOPA AND APOMORPHINE BY MK-801 IN THE RESERPINE-TREATED MOUSE

In 24 h reserpine-treated akinetic mice, locomotion was induced by the D-1-selective agonist SKF 38393 (30 mg/kg IP), or by the mixed D-1/D-2 agonists L-DOPA (150 mg/kg IP, plus benserazide 100 mg/kg IF) and apomorphine (0.5 mg/kg SC). The non-competitive NMDA receptor antagonist MK 801 (0.01-1.6 mg/kg IP) did not induce motor activity by itself, but potentiated the motor responses to L-DOPA and apomorphine at roughly 10-fold lower doses than those which facilitated D-1 responding. These data cast doubt on the notion that glutamate antagonists enhance the antiparkinsonian efficacy of mixed D-1/D-2 agonists solely through a D-1 receptor mechanism.