Schindler Charles W, Carmona Gilberto N
Preclinical Pharmacology Section, NIH/NIDA Intramural Research Program, Baltimore, MD 21224, USA.
Pharmacol Biochem Behav. 2002 Jul;72(4):857-63. doi: 10.1016/s0091-3057(02)00770-0.
Male and female Sprague-Dawley rats were treated with cocaine, the specific dopamine uptake inhibitor GBR 12909, the dopamine D1 agonist SKF 82958 or the dopamine D2 agonist quinpirole. After treatment, the rats were placed in an activity chamber for 30 min and locomotor activity was monitored. Cocaine, GBR 12909 and SKF 82958 all increased locomotor activity in both males and females, but greater increases were observed in females. In contrast, quinpirole produced decreases in activity, with males showing greater decreases than females. Separate groups of animals were given SCH 23390 or eticlopride prior to cocaine. The D1 antagonist SCH 23390 reduced the locomotor activating effects of cocaine in both males and females, with females showing greater sensitivity to SCH 23390. The D2 antagonist eticlopride also reduced the locomotor activating effects of cocaine, with no clear differences between males and females. These results suggest that the differences between males and females in their locomotor response to cocaine can be at least partially attributed to differences in the function of dopamine D1 and D2 receptors.
将雄性和雌性斯普拉格-道利大鼠分别用可卡因、特异性多巴胺摄取抑制剂GBR 12909、多巴胺D1激动剂SKF 82958或多巴胺D2激动剂喹吡罗进行处理。处理后,将大鼠置于活动箱中30分钟,并监测其运动活性。可卡因、GBR 12909和SKF 82958均增加了雄性和雌性大鼠的运动活性,但在雌性大鼠中观察到的增加幅度更大。相比之下,喹吡罗使活性降低,雄性大鼠的降低幅度大于雌性大鼠。在给予可卡因之前,将单独的动物组给予SCH 23390或依托必利。D1拮抗剂SCH 23390降低了可卡因对雄性和雌性大鼠的运动激活作用,雌性大鼠对SCH 23390表现出更高的敏感性。D2拮抗剂依托必利也降低了可卡因的运动激活作用,雄性和雌性大鼠之间没有明显差异。这些结果表明,雄性和雌性大鼠对可卡因运动反应的差异至少部分归因于多巴胺D1和D2受体功能的差异。