Morissette M, Lévesque D, Di Paolo T
School of Pharmacy, Laval University, Quebec, Canada.
Mol Pharmacol. 1992 Sep;42(3):480-8.
Quantitative autoradiography was used to investigate dopamine receptor repopulation kinetics after irreversible dopamine receptor inactivation with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ). The striatum and substantia nigra of two groups of ovariectomized female rats were compared. One group of rats was pretreated with estradiol (10 micrograms, twice daily, for 2 weeks), and another group received the vehicle. Striatal D1 dopamine receptors had larger degradation and production rate constants, compared with D2 receptors. The D2 receptor degradation rate constant increased rostro-caudally in the striatum of vehicle-treated rats, whereas this was not observed for estradiol-treated animals. A trend similar to that for D2 receptors was observed for the D1 receptor degradation rate constant in the striatum of vehicle-treated rats, whereas in estradiol-treated animals this constant decreased rostro-caudally. In the anterior and the middle parts of the striatum D2 receptor recovery parameters were not affected by chronic estradiol treatment, but in the posterior part estradiol-treated rats had lower receptor degradation and production rate constants. In the anterior part of the striatum, chronic estradiol treatment did not affect the recovery parameters of D1 receptors, whereas lowered receptor degradation and production rate constants were observed in the middle and posterior parts. D1 receptor recovery parameters in the substantia nigra were not affected by chronic estradiol treatment. After EEDQ administration to vehicle-treated rats, striatal dopamine levels decreased gradually, to reach a minimum 4 days later, and returned to control values after 7 days. In estradiol-treated rats, however, dopamine levels increased 2 days after EEDQ. Levels of the dopamine metabolites dihydroxyphenylacetic acid and homovanillic acid increased in the striatum after EEDQ administration in vehicle-treated rats. Even greater increases that lasted longer were observed in estradiol-treated rats after EEDQ. Striatal levels of serotonin and its metabolite 5-hydroxyindoleacetic acid were not significantly affected by EEDQ or estradiol administration. In summary, estradiol decreased striatal D1 and D2 receptor degradation rate constants, with the greatest effect being observed in the caudal part of the striatum. EEDQ dopamine receptor inactivation also revealed an increase of dopamine and its metabolites in the striatum after estradiol treatment.
采用定量放射自显影术研究用N - 乙氧羰基 - 2 - 乙氧基 - 1,2 - 二氢喹啉（EEDQ）使多巴胺受体不可逆失活后多巴胺受体的再填充动力学。比较了两组去卵巢雌性大鼠的纹状体和黑质。一组大鼠用雌二醇预处理（10微克，每日两次，共2周），另一组给予溶媒。与D2受体相比，纹状体D1多巴胺受体具有更大的降解和生成速率常数。在给予溶媒的大鼠纹状体中，D2受体降解速率常数从吻侧到尾侧增加，而在给予雌二醇的动物中未观察到这种情况。在给予溶媒的大鼠纹状体中，D1受体降解速率常数观察到与D2受体类似的趋势，而在给予雌二醇的动物中，该常数从吻侧到尾侧降低。在纹状体的前部和中部，慢性雌二醇处理不影响D2受体的恢复参数，但在后部，给予雌二醇的大鼠受体降解和生成速率常数较低。在纹状体前部，慢性雌二醇处理不影响D1受体的恢复参数，而在中部和后部观察到受体降解和生成速率常数降低。黑质中D1受体恢复参数不受慢性雌二醇处理影响。给给予溶媒的大鼠注射EEDQ后，纹状体多巴胺水平逐渐下降，4天后降至最低，7天后恢复到对照值。然而，在给予雌二醇的大鼠中，EEDQ后2天多巴胺水平升高。给予溶媒的大鼠注射EEDQ后，纹状体中多巴胺代谢物二羟基苯乙酸和高香草酸水平升高。在给予雌二醇的大鼠注射EEDQ后观察到更大且持续时间更长的升高。EEDQ或雌二醇给药对纹状体中5 - 羟色胺及其代谢物5 - 羟基吲哚乙酸水平无显著影响。总之，雌二醇降低了纹状体D1和D2受体降解速率常数，在纹状体尾部观察到最大效应。EEDQ使多巴胺受体失活还显示出雌二醇处理后纹状体中多巴胺及其代谢物增加。
