Involvement of dopamine D1 and D2 receptors in Fos immunoreactivity induced by stepholidine in both intact and denervated striatum of lesioned rats

Stepholidine (SPD), a natural product, has been demonstrated in previous studies as a D-1 agonist and D-2 antagonist. In this work SPD-induced Fos immunoreactivity was examined. In the normal rats, Fos was induced in the striatum by SPD (1-20 mg/kg, ip) dose-dependently. The distribution 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 labeled with horseradish peroxidase (HRP) from GP but not from SN, and could 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 the 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. Similar 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 retrogradely labeled from SN but not from GP. Furthermore, this expression was prevented by the pretreatment of SCH23390 (0.2 mg/kg, ip) but not LY171555, suggesting that the Fos expression in denervated side was due to the D-1 agonistic action of SPD. Therefore, we concluded that the Fos expression induced by SPD in intact and denervated striatum was mediated via D-2 and D-1 receptor respectively, supporting the previous standpoint that SPD possesses the dual action, i.e antagonist to D-2 and agonist to D-1 receptors. Furthermore, it is suggested that the contralateral turning behavior induced by SPD may result from the D-1-mediated excitation of striatonigral neurons of the denervated side of the lesioned rats.