糖皮质激素受体对大鼠丙泊酚依赖行为的影响及其机制

目的：研究糖皮质激素受体（GR）对大鼠丙泊酚觅药行为的影响，探讨丙泊酚精神依赖性的发生机制。方法：24 只SD大鼠用固定比率（FR1）强化程序建立丙泊酚精神依赖性模型，并随机均分为对照组、RU486 10 mg/kg组、RU486 20 mg/kg组和RU486 40 mg/kg组，观察腹腔注射不同剂量GR拮抗剂RU486对大鼠自身觅药行为学的影响，Western blot检测大鼠伏隔核（NAc）内多巴胺转运体（DAT）的蛋白表达水平。另取24 只SD大鼠用FR1程序建立自身给予蔗糖行为模型后随机均分为对照组、RU486 10 mg/kg组、RU486 20 mg/kg组和RU486 40 mg/kg组，观察腹腔注射不同剂量GR拮抗剂RU486 对大鼠自身给予蔗糖行为的影响。结果：与对照组比，GR拮抗剂RU486 腹腔给药可剂量依赖性减弱大鼠丙泊酚自身觅药行为（P ＜0.01），并降低大鼠NAc内DAT的蛋白水平表达（P ＜0.05）。与对照组比，RU486 腹腔给药不影响大鼠自身给予蔗糖行为（P ＞0.05）。结论：GR拮抗剂可能通过影响NAc内DAT水平从而减弱大鼠丙泊酚觅药行为。

The effect of glucocorticoid receptor on propofol self-administration of rats and its mechanisms

Objective: To determine whether glucocorticoid receptor involves in propofol self-administration of rats, so as to offer reference for clinical prevention and treatment. Methods: In one experimental group, twenty-four Sprague-Dawley rats were trained to self-administer propofol under a fixed ration (FR1) schedule of reinforcement for 14 d. Then, the rats were treated with saline (control group) and RU486, a GR antagonist (10,20, 40 mg/kg) at 1 h prior to the last training to observe the change of animal behavior. Western blot was used to detect the dopamine DAT level in NAc of propofol dependent. In the other experimental group, twenty-four rats were trained to nose-poke for sucrose pellets under FR1 schedule of reinforcement of a daily 0.5-h session for successive 7 days. Thenthe trained rats received intraperitoneally either saline or a dose of RU486 (10, 20,40 mg/kg) at 1 h prior to the last training to observe the change of animal behavior. Results: RU486 significantly decreased the number of injections and active responses (P<0.01), which was associated with the large decrease in DAT of NAc (P<0.05). However, the food-maintaining sucrose responses under FR1 schedule was not affected by any doses of RU486 tested (P>0.05). Conclusion: The present results indicate that RU486 may counteract thereinforcing properties of propofol, playing an important role in the incubation of propofol dependent by influencing the dopamine DAT levels.