MK-801 potentiates dopaminergic D1 but reduces D2 responses in the 6-hydroxydopamine model of Parkinson's disease

The D1 agonist, SKF 38393, failed to induce contralateral turning in drug-naive rats lesioned unilaterally with 6-hydroxydopamine from 17 days. Priming with a dopamine agonist, such as the D2 agonist, LY 171555, three days before, made SKF 38393 fully effective in inducing contralateral turning. Analysis of D1 receptor binding in striata of drug-naive and primed rats showed no change in the Bmax and Kd. In contrast, dopamine-stimulated adenylate cyclase showed a decrease in its Km for dopamine in the lesioned side of primed rats as compared with drug-naive rats. Thus, priming appears to elicit changes at the level of the transduction mechanism of D1 receptors rather than in the D1 recognition site itself