(-)-stepholidine: a dopamine receptor antagonist shows agonistic effect on rotational behavior in 6-hydroxydopamine-lesioned rats.

(-)-Stepholidine ((-)-SPD), a well demonstrated dopamine (DA) receptor antagonist in normal rats, could markedly induce contralateral rotational behavior in 6-hydroxydopamine (6-OHDA)-lesioned rats. This peculiar behavioral action of (-)-SPD, proposed to be an agonistic action on DA receptors, was further studied in this paper. The rotational behavior challenged by (-)-SPD (4 mg.kg-1, ip) or SKF-38393 (selective D1 agonist) had a gradually progressive process with a long latent period and a plateau response after 56-67 postlesion days. On the contrary, the action of apomorphine (APO) or D2 selective agonist N-0347, had a short latent period and a plateau response after d 21 of postlesion. In the latent period of rotation, (-)-SPD (4 mg.kg-1) was primed by pretreatment of APO (0.2 mg.kg-1, ip). In the period of steady contralateral rotation, a dose-dependent action of (-)-SPD was found in a range of 0.5-8 mg.kg-1 and a linear correlation (r = 0.77, P less than 0.01) between the rotation induced by (-)-SPD (4 mg.kg-1) and by APO (0.2 mg.kg-1) was also shown. These results suggest that the agonistic effect of (-)-SPD on rotation behavior in 6-OHDA-lesioned rats resembles that of D1 agonist SKF-38393. Taken together, the dual actions of (-)-SPD, antagonistic on normosensitive DA receptors and agonistic on supersensitive DA receptors, were proposed.