The kappa-opioid receptor agonist spiradoline differentially alters the rotational response to dopamine D1 and D2 agonists.

The effect of the selective kappa-opioid agonist, spiradoline, on rotational behavior induced by a dopamine D1 or D2 agonist was examined in rats with a unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway. Spiradoline reduced the rotational response to the D1 agonist SKF 38393 in a dose-dependent manner. Spiradoline had no effect on the total number of turns elicited by the D2 agonist quinpirole, but did alter the pattern of quinpirole-induced rotation at the highest dose tested. By itself, spiradoline did not have any obvious effects on motor behavior and did not cause rotation in either the ipsilateral or contralateral direction. These data suggest that kappa receptor stimulation, possibly mediated by the endogenous agonist dynorphin under physiological conditions, may function to dampen striatal output through the D1 receptor-regulated striatonigral pathway.