CHRONIC TREATMENT WITH (-)-STEPHOLIDINE ALTERS DENSITY AND TURNOVER OF D-1 AND D-2 RECEPTORS IN STRIATUM

AIM: To study the effects of chronic administration of SPD on the dens ity and turnover of striatal D-1 and D-2 dopamine (DA) receptors. METH ODS: Receptor density was monitored by radio-receptor binding assay. T he receptor recovery and turnover were studied after irreversible inac tivation by N-ethoxycarbonyl-2-ethoxy-1,2-dihydro-quinoline (EEDQ). RE SULTS: Chronic SPD treatment (sc, 20 mg . kg(-1). d(-1) x 21 d) upregu lated both striatal D-1 and D-2 receptor density. As compared to vehic le-treated rats, SPD increased D-1 and D-2 receptors by 41.5 % and 43. 7 %, respectively. SPD also altered the turnover of both D-1 and D-2 r eceptors. The degradation rate constant (k = 0.0082 . h(-1)) and the s ynthesis rate (r = 2.65 pmol . h(-1)/g protein) of D-2 receptors in SP D-treated rats were significantly increased vs vehicle-treated rats (k = 0.0049 . h(-1); r = 1.10 pmol . h(-1)/g protein). The degradation r ate constant (k = 0.0059 . h(-1)) and the synthesis rate (r = 3.1 pmol . h(-1)/g protein) of D, receptors was also increased in SPD-treated rats vs vehicle-treated rats (k = 0.0048 . h(-1); r = 1.8 pmol . h(-1) /g protein), but the alteration of degradation rate constant missed si gnificance (P > 0.05). As a result, receptor recovery following EEDQ w as accelerated. The half time for D-1 and D-2 receptors recovery in SP D group were 117.5 h and 84.5 h, respectively, shorter than 144.4 h an d 141.4 h in vehicle-treated rats. CONCLUSION: Chronic SPD treatment u pregulated D-1 and D-2 receptors, and accelerated DA receptor turnover and recovery mainly by increasing receptor synthesis.