Abstract

The potential antiparkinson activity of N-methyl-D-aspartate antagonists was investigated by examining the effects of dizocilpine (MK-801) on rats with 6-hydroxydopamine-induced lesions of the nigrostriatal pathway. MK-801, when administered alone to these animals, elicited ipsilateral rotation, which could be blocked by haloperidol. MK-801, at doses that did not produce rotation when given alone, inhibited the contralateral rotation produced by the D2 receptor agonist quinpirole but had no effect on the rotation induced by the D1 agonist SKF 38393 [(+-)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8- diolhydrochloride]. However, exposure to levodopa 3 days previously resulted in a subsensitive rotational response to SKF 38393 and this subsensitivity to the D1 agonist was reversed by MK-801. The subsensitive rotational response to SKF 38393 was not evident 7 days after exposure to levodopa and MK-801 had no effect on the response to SKF 38393 at this time. These data suggest that N-methyl-D-aspartate receptor blockade can exert differential effects on dopamine agonist-induced rotational behavior that depend on which dopamine receptor subtype is activated and the previous exposure of the animal to dopamine agonists.