MK-801 reverses effects of chronic levodopa on D1 and D2 dopamine agonist-induced rotational behavior

The effect of dizocilpine (MK-801) on dopaminergic agonist-induced rotational behavior was investigated in rats with 6-hydroxydopamine lesions of the nigrostriatal pathway after chronic administration of levodopa. The rotational response to the D2 agonist quinpirole was markedly increased in levodopa-treated animals compared with rats chronically administered saline. The increase in responsiveness to quinpirole was reversed by co-administered MK-801. Conversely, the rotational response to the D1 agonist SKF 38393 was reduced following chronic treatment with levodopa. The decrease in response to SKF 38393 was also reversed by MK-801. Chronic treatment with levodopa failed to alter the rotational responses to two other D1 preferring agonists SKF 81297 and SKF 82968, but responses to both agonists were increased by the co-administration of MK-801. These data support the hypothesis the MK-801 may reverse the differential changes in D1 and D2 agonist-induced motor responses which result from chronic treatment with levodopa.