Comparison of (-)-stepholidine and D1 or D2 agonists on unit firing of globus pallidus in 6-hydroxydopamine-lesioned rats

(-)-Stepholidine(SPD), isolated from the Chinese herb Stephania, is demonstrated to be a DA antagonist, but it also shows D-1 agonistic action on rotational behavior in unilateral 6-hydroxydopamine (6-OHDA) lesioned rats. The present study further ascertains its D-1 agonistic property on firing activity of globus pallidus (GP) in control and 6-OHDA-lesioned rats. In the control rats, the firing activities of the GP neurons elicited by DA agonists (i.v.), such as apomorphine (D-1/D-2), SKF38393 (D-1), and LY171555 (D-2), were readily reversed by SPD (4 mg/kg, i.v.); but SPD, per se, induced variable alterations. In the 6-OHDA-lesioned rats, apomorphine, SKF38393 and LY171555 displayed the marked inhibition as well as excitation on the unit firing. The individual firing variations (87.1+/-17.8, 55.1+/-15.7 and 62.1+/-16.7%, respectively) were much larger than those in the control group, and were completely abolished by SPD (2 mg/kg). However, SPD also showed D-1 partial agonistic action on the GP neuron firing. Moreover, the pre-blockade of D-2 receptors with spiperone (0.5 mg/kg, i.v.), SPD exhibited the D-1 agonist action which was reversed by the D-1 antagonist SCH23390. These results suggest that SPD has a dual action on the GP neuron firing in the 6-OHDA-lesioned rats, i.e., antagonist to D-2 DA receptors and partial agonist to D-1 receptors.