Bradberry C W, Lory J D, Roth R H
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510.
J Neurochem. 1991 Mar;56(3):748-52. doi: 10.1111/j.1471-4159.1991.tb01987.x.
The effect of the anxiogenic beta-carboline methyl-beta-carboline-3-carboxyamide (FG 7142) on dopamine release in prefrontal cortex and striatum in the awake freely moving rat was determined using the technique of microdialysis. FG 7142 (25 mg/kg, i.p.) caused a time-dependent increase in dopamine release in prefrontal cortex which was statistically significantly greater than the response to vehicle administration. Dopamine release in striatum was unaltered by FG 7142. Pretreatment of animals with the benzodiazepine antagonist Ro 15-1788 (30 mg/kg, i.p., 15 min prior to FG 7142 administration) completely abolished the increase in dopamine release caused by FG 7142 in prefrontal cortex. These data indicate that the anxiogenic benzodiazepine inverse agonist FG 7142 can selectively increase dopamine release in prefrontal cortex, and that this effect appears to be mediated via the gamma-aminobutyric acid/benzodiazepine receptor complex.
采用微透析技术测定了致焦虑性β-咔啉甲基-β-咔啉-3-羧酰胺(FG 7142)对清醒自由活动大鼠前额叶皮质和纹状体中多巴胺释放的影响。FG 7142(25毫克/千克,腹腔注射)导致前额叶皮质中多巴胺释放呈时间依赖性增加,在统计学上显著大于对给予赋形剂的反应。FG 7142未改变纹状体中的多巴胺释放。用苯二氮䓬拮抗剂Ro 15 - 1788(30毫克/千克,腹腔注射,在给予FG 7142前15分钟)对动物进行预处理,完全消除了FG 7142引起的前额叶皮质中多巴胺释放的增加。这些数据表明,致焦虑性苯二氮䓬反向激动剂FG 7142可选择性增加前额叶皮质中的多巴胺释放,且这种作用似乎是通过γ-氨基丁酸/苯二氮䓬受体复合物介导的。