MOTOR-RESPONSES TO DOPAMINE-D1 AND DOPAMINE-D2 AGONISTS IN THE RESERPINE-TREATED MOUSE ARE AFFECTED DIFFERENTIALLY BY THE NMDA RECEPTOR ANTAGONIST MK-801

The akinesia induced by reserpine in mice was effectively reversed by the dopamine D1 receptor agonists SKF 38393 (5-30 mg/kg IP) and CY 208-243 (1-5 mg/kg IP), and by the mixed D1/D2 agonist pergolide (5 mg/kg SC), but less well by the D2 agonists lisuride, PHNO, LY 171555 and RU 24213 (each at 5 mg/kg SC) and not at all by the NMDA receptor antagonist MK 801 (0.1-10 mg/kg IP). MK 801 potentiated D1-dependent locomotion, but always suppressed rearing and grooming. D2-dependent locomotion was inhibited by MK 801. The D2 agonist RU 24213 was antagonised by as little as 6.25-mu-g/kg MK 801, while PHNO and LY 171555 were antagonised by 0.1 mg/kg MK 801. Lisuride was not inhibited by up to 1.6 mg/kg MK 801. Importantly, all animals showed signs of incapacitation with MK 801 in certain elements of their behaviour, most notably ataxia and hind limb abduction. Thus whilst NMDA receptor blockade can facilitate the restoration of movement by dopamine D1 (though not D2) agonists in monoamine-depleted mice, the fluency of the motor response is adversely affected.