Wilmot C A, Szczepanik A M
Department of Biological Research, Hoechst-Roussel Pharmaceuticals Inc., Somerville, NJ 08876.
Brain Res. 1989 May 22;487(2):288-98. doi: 10.1016/0006-8993(89)90833-0.
The effects of acute and chronic treatments with haloperidol or clozapine on the binding of [3H]spiperone to D2 and 5-HT2 receptors were examined in 6 discrete regions of the striatum, n. accumbens and frontal cortex using quantitative autoradiography. Acute treatment with haloperidol, 0.1-2.0 mg/kg, i.p., produced a dose-dependent reduction to 60% of control in the binding of [3H]spiperone to D2 receptors in the striatum and n. accumbens and no effect on the binding of [3H]spiperone to 5-HT2 receptors in the striatum, n. accumbens or frontal cortex. Acute treatment with clozapine, 10-40 mg/kg, i.p., produced a dose-dependent reduction in D2-specific binding in both the n. accumbens and the striatum and also significant reductions to 24% of control in the binding of [3H]spiperone to cortical 5-HT2 receptors. Chronic treatment with haloperidol, 1 mg/kg/day, i.p., significantly increased (40-65%) the maximal number of D2-specific [3H]spiperone binding sites in the n. accumbens and the dorsolateral and ventrolateral regions of the striatum, whereas small increases (20-29%) were seen in the ventromedial, dorsomedial, rostral and caudal regions of the striatum. Chronic treatment with clozapine, 20 mg/kg/day, i.p., did not change the maximal number of D2 receptors in the n. accumbens or any region of the striatum. Chronic treatments with clozapine produced a decrease in the maximal number of cortical 5-HT2 receptors to 55% of control whereas haloperidol had no effect. This study demonstrates regional differences in the up-regulation of striatal D2 receptors following chronic treatment with haloperidol and different effects of a typical and atypical neuroleptic on 5-HT2 receptors following acute and chronic treatments.
使用定量放射自显影技术，研究了氟哌啶醇或氯氮平急性及慢性治疗对纹状体、伏隔核和额叶皮质6个离散区域中[3H]螺哌隆与D2和5-HT2受体结合的影响。腹腔注射0.1 - 2.0mg/kg氟哌啶醇进行急性治疗，可使纹状体和伏隔核中[3H]螺哌隆与D2受体的结合呈剂量依赖性降低至对照的60%，而对纹状体、伏隔核或额叶皮质中[3H]螺哌隆与5-HT2受体的结合无影响。腹腔注射10 - 40mg/kg氯氮平进行急性治疗，可使伏隔核和纹状体中D2特异性结合呈剂量依赖性降低，并且使皮质中[3H]螺哌隆与5-HT2受体的结合显著降低至对照的24%。腹腔注射1mg/kg/天氟哌啶醇进行慢性治疗，可使伏隔核以及纹状体的背外侧和腹外侧区域中D2特异性[3H]螺哌隆结合位点的最大数量显著增加（40 - 65%），而在纹状体的腹内侧、背内侧、嘴侧和尾侧区域则有小幅增加（20 - 29%）。腹腔注射20mg/kg/天氯氮平进行慢性治疗，并未改变伏隔核或纹状体任何区域中D2受体的最大数量。氯氮平慢性治疗可使皮质5-HT2受体的最大数量减少至对照的55%，而氟哌啶醇则无此作用。本研究证明了氟哌啶醇慢性治疗后纹状体D2受体上调的区域差异，以及典型和非典型抗精神病药物在急性和慢性治疗后对5-HT2受体的不同影响。
