Dual actions of (-)-stepholidine on dopamine receptor subtypes after substantia nigra lesion

1. It was found that the contralateral rotation challenged by (-)-SPD (4 mg/kg, ip) in 6-OHDA-lesioned rats had a gradually progressive process with long latent period and a maximal response on 63 days after lesion. This steady contralateral rotation was preferably antagonized by D-1 antagonist SCH23390 than D-2 antagonists. During its latent period (-)-SPD exhibited the antagonistic effect to APO, while during its period of full response (-)-SPD could potentiate the APO-induced rotation. 2. In the rats lesioned with kainic acid plus 6-OHDA to destroy the SNC and SNR, (-)-SPD and SKF-38393 challenged neither contralateral nor ipsilateral rotation, while APO still induced the rotation but towards ipsilateral side, just opposite to that in 6-OHDA-lesioned rats. In this case, (-)-SPD antagonized the response to APO as did SCH 23390. 3. These evidences suggest that the agonistic action of (-)-SPD is resulted from D-1 receptor subtype at the SNR under supersensitive functional state. The fact that SNR lesion could completely eliminate the agonistic action of (-)-SPD further indicate that the D-1 receptors in the ipsilateral SNR may be the sites of action of (-)-SPD. The dual actions of (-)-SPD are dependent upon the supersensitivity of D-1 receptor subtypes which render the antagonistic action to convert into the agonistic.