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目的:研究咪哒唑仑对小鼠和大鼠吗啡戒断反应的影响.方法:实验中采用急性和慢性吗啡依赖和纳洛酮催促戒断模型.使用放免法测定cAMP含量,免疫组织化学方法观察Fos蛋白表达变化.结果:合用咪哒唑仑和吗啡可抑制小鼠急性和慢性吗啡依赖的发展.在急性吗啡依赖小鼠,咪哒唑仑-吗啡组纳络酮催促跳跃的ED_(50)(10.4,8.5-12.3 mg/kg)明显大于生理盐水-吗啡组(3.0,1.9-4.3 mg/kg)(P<0.01).在慢性吗啡依赖小鼠,咪哒唑仑-吗啡组纳络酮催促跳跃的发生率和跳跃次数明显低于生理盐水-吗啡组(P<0.01).预先使用咪哒唑仑抑制吗啡戒断大鼠脊髓Fos蛋白表达,但不能抑制脊髓cAMP含量的增加.结论:咪哒唑仑通过抑制脊髓神经元敏感化减轻吗啡戒断反应,cAMP信号转导通路不参与介导这一效应.
OBJECTIVE: To study the effect of midazolam on morphine withdrawal in mice and rats.Methods: Acute and chronic morphine dependence and naloxone were used in the experiment to induce withdrawal.CAMP content was measured by radioimmunoassay, immunohistochemistry The changes of Fos protein expression were observed.Results: Midazolam combined with morphine inhibited the development of acute and chronic morphine dependence in mice.In acute morphine-dependent mice, midazolam of midazolam-morphine group promoted ED_ (50 ) (10.4, 8.5-12.3 mg / kg) were significantly higher than those in normal saline-morphine group (3.0,1.9-4.3 mg / kg, P <0.01) .In chronic morphine dependent mice, midazolam- The incidence of hops and the number of jumps were significantly lower than those of saline-morphine group (P <0.01) .Premedial use of midazolam inhibited the expression of Fos protein in the spinal cord of morphine-withdrawal rats, but did not inhibit the increase of cAMP content in the spinal cord. : Midazolam inhibits morphine withdrawal response through inhibition of spinal cord sensitization, and cAMP signaling pathway is not involved in mediating this effect.