INVOLVEMENT OF DOPAMINE D-1 AND D-2 RECEPTORS IN FOS IMMUNOREACTIVITYINDUCED BY STEPHOLIDINE IN BOTH INTACT AND DENERVATED STRIATUM OF LESIONED RATS

Stepholidine (SPD), a natural product, has been demonstrated in previo us studies as a D-1 agonist and D-2 antagonist. In this work SPD-induc ed Fos immunoreactivity was examined. In the normal rats, Fos was indu ced in the striatum by SPD (1-20 mg/kg, ip) dose-dependently. The dist ribution of Fos-positive cells induced by SPD showed a rostral-caudal decline, matching the distribution of D-2 dopamine receptors. The Fos- positive cells were mainly found in striatal neurons retrogradely labe led with horseradish peroxidase (HRP) from GP but not from SN, and cou ld be abolished by the pretreatment of a D-2 agonist LY171555 (2 mg/kg , ip), suggesting that the Fos expression in normal rats was due to th e D-2 antagonistic action of SPD. In the unilateral 6-hydroxydopamine- lesioned rats, SPD (4 mg/kg, ip) induced Fos expression in intact and denervated side of the striatum with different characteristics. Simila r to that of normal rats, the Fos expression in intact side possessed the rostral-caudal gradient and could be abolished by the pretreatment of LY171555. However, in the denervated side, the Fos positive cells were widely distributed, and mainly found in striatal neurons retrogra dely labeled from SN but not from GP. Furthermore, this expression was prevented by the pretreatment of SCH23390 (0.2 mg/kg, ip) but not LY1 71555, suggesting that the Fos expression in denervated side was due t o the D-1 agonistic action of SPD. Therefore, we concluded that the Fo s expression induced by SPD in intact and denervated striatum was medi ated via D-2 and D-1 receptor respectively, supporting the previous st andpoint that SPD possesses the dual action, i.e antagonist to D-2 and agonist to D-1 receptors. Furthermore, it is suggested that the contr alateral turning behavior induced by SPD may result from the D-1-media ted excitation of striatonigral neurons of the denervated side of the lesioned rats.