摘要
目的 谷氨酸NMDA受体拮抗剂地卓西平（MK801）对大鼠急性吗啡依赖戒断性情绪反应的影响。方法 以条件性位置厌恶（CPA）实验建立急性吗啡依赖大鼠戒断性情绪反应模型，观察大鼠训练前后在“纳络酮匹配侧”停留时间的变化。结果 吗啡（5．6mg．kg^-1）纳络酮（0．5mg．kg^-1）间隔4h皮下注射，进行2轮纳络酮匹配训练，能建立稳定的急性吗啡依赖戒断诱发的CPA模型；注射纳络酮前30min分别注射生理盐水和不同剂量的MK801（0．05mg．kg^-1；0．1mg．kg^-1），3组大鼠在“纳络酮匹配侧”停留时间训练前、后分别是[（447．25±47．99）SVS（238．00±20．56）S]；[（454．63±44．04）SVS（395．38±55．95）S]；[（450．38±51．37）SVS（419．63±52．88）S]，Post Hoe Tests表明只有空白对照组的训练前后差异显著，而MK801干预的2组训练前后并无显著差异。对急性吗啡依赖和未接触吗啡的大鼠注射MK801，4组大鼠在“处理侧”停留时间训练前后组间和组内均无显著差异，即该剂量的MK801不具有奖赏效应。结论 MK801阻断了CPA的获得可能是直接抑制戒断时厌恶性情绪反应而非其本身具有奖赏效应，提示谷氨酸NMDA受体是介导急性吗啡依赖戒断性情绪反应的部分神经机制。
Objective To investigate the effect of NMDA receptor antagonist MK801 on the negative affection induced by withdrawal from acute morphine dependence in rats. Methods The conditioned place aversion （CPA） was used to establish the negative affection induced by withdrawal from acute morphine dependence in rats. Results Significant place aversion were successfully established by two pairings of acutely administering morphine （5.6 mg. kg^-1 , SC） followed 4h later by naloxone （0.5 mg. kg^-1 , SC）. Compared with control group, MK801 （0.05 mg. kg^-1 and 0.1 mg. kg^-1, SC） administered 30min before conditioning significantly inhibited the acquisition of the CPA. The time spent in the naloxone-paired compartment before and after conditioning were as followed （447.25 ±47.99） vs （238.00 ±20.56） ; （454.63±44.04） vs （395.38 ±55.95） ; （450.38 ±51.37 ） vs （419.63 ±52.88 ） for three groups respectively. Post Hoc Tests indicated that significant difference in time spent in the naloxone-paired compartment before and after conditioning only for control group showing that naloxone induced CPA. But this difference were not present in the groups which received MK801 indicting that MK801 inhibited the acquisition of CPA. The doses of MK801 used in this experiment produced no place conditioning by themselves in either morphine-naive or morphine-exposed subjects. Conclusion Those data suggested a possible involvement of NMDA receptor in the negative affective components induced by withdrawal from acute morphine treated rats.
出处
《中国行为医学科学》
CSCD
2007年第4期315-317,共3页
Chinese Journal of Behavioral Medical Science
基金
国家重点基础研究发展计划（973计划）资助项目（CB515404）
国家自然科学基金资助项目（30230130）
