东莨菪碱对吗啡诱导的大鼠行为敏感化的影响

Effects of Scopolamine on Behavioral Sensitization Induced by Morphine in Rats

药物重复处理导致的行为敏感化与成瘾过程密切相关。本实验检验东莨菪碱对吗啡诱导的大鼠行为敏感化发展和转化的影响。实验-动物分为3组，分别进行生理盐水（对照组）、吗啡（10mg／ks，吗啡组）、吗啡（10mg／ks）＋东莨菪碱（3mg／ks，吗啡-东莨菪碱组）前处理，36h腹腔注射4次（第1—2天）。自然戒断7天（第3—9天）。第10天，所有动物均使用吗啡（4mg／kg）激发，记录动物的自发活动量；第2，4天，吗啡组和吗啡-东莨菪碱组动物重复第10天的操作。实验二动物分为3组，分别接受生理盐水（对照组）、吗啡（10mg／kg，吗啡组）、吗啡（10mg／kg，吗啡-东莨菪碱组）处理，36h腹腔注射4次（第1～3天）；间隔12h后，3组动物分别接受生理盐水、生理盐水和东莨菪碱（3mg／kg）处理，仍为36h腹腔注射4次（第3～5天）。第6～9天不进行药物处理。第10天和第17天，分别使用吗啡（4mg／ks）激发，记录动物的活动量。记录时间均为两小时（10min为一个记录单元）。结果表明，东莨菪碱能够抑制吗啡诱导的行为敏感化的发展，一定程度上也能够延缓行为敏感化的转化但没有阻断这种转化。

Introduction Behavioral sensitization, which has some common properties with learning, memory and long- term potentiation （LTP）, is thought to play a key role in certain aspects of drug addiction such as compulsive drugseeking behavior. It has been demonstrated that behavioral sensitization to amphetamine is blocked by glutamatergic N - methyl- D - aspartate （NMDA） receptor antagonist MK801 ,which has been proved to block learning, memory and LTP. Scopolamine, an antasonist of muscarinic cholinergic receptor, has also bccn known to inhibit learning, memory and LTP. However, whereas several studies have showed that scopolamine blocks behavioral sensitization to drubs of abuse, others have suggested that scopolamine plays the role of potentiation to it. This conflict led us to examine further the effects of scopolamine on the development as well as the transfer of behavioral sensitization induced by morphine. Method Experiment 1 ： Rats were given four saline ＋ saline （control group） or 10 - mg/kg morphine ＋ saline （morphine group） or 10 - mg/kg morphine ＋ 3 - mg/kg scopolamine （morphine - scopolamine group） injections （i.p.） over a 36 - h period （days 1 -2）, followed by a 7 - days withdrawal period （days 3 -9）. On day 10, all animals were challenged with 4 - mg/kg morphine （i.p.） and their locomotor activity was measured for two hours. On day 24, morphine group and morphine - scopolamine group were challenged with 4 - mg/kg morphine again. Experiment 2： Rats were given four saline （control group） or 10 - mg/kg morphine （morphine group） or 10 - mg/kg morphine （morphine-scopolamine group） injections （i.p.） over a 36 - h period （days 1 -3）. After a 12 - hour＇s interval, control group and morphine group were administered with four saline and morphine - scopolamine group with four 3 - mg/kg scopolamine over a 36- h period （day 3 -5）, followed by a 4- days withdrawal period （days 6 -9）. On day 10 and 17, all animals were challenged with 4 - mg/kg morphine and their locomotor activity was measured for two hours. Results In Experiment I, rats in morphine group showed significantly greater locomotor activity than other two groups （control group and morphine- scopolamine group） on day l0 and than morphine- scopolamine group on day 24. In Experiment 2, there was significant difference between the locomotor activity of morphine group and that of control group on day 10, but morphine - scopolamine group had no significant difference compared with control group or with morphine group. On day 17, the locomotor activity of morphine - scopolamine group significantly in,eased compared with control group and had no significant difference compared with morphine group. Conclusions The results of this study showed that scopolamine could inhibit the development of sensitization and delay to a certain extent but could not inhibit transfer of sensitization induced by morphine.