NOS抑制剂和MK-801对吗啡依赖大鼠脊髓和脑干毒蕈碱型受体表达的影响

Effects of NOS inhibitor and NMDA receptor antagonist on the expression of muscarinic receptors in spinal cord and brainstem during morphine withdrawal in rats

目的 观察NMDA受体拮抗剂和NOS抑制剂对吗啡依赖大鼠毒蕈碱型乙酰胆碱受体亚型表达的影响。方法 RT PCR方法检测m1 5mRNA水平。结果 吗啡依赖大鼠脊髓注射纳洛酮 1h后脊髓m1 、m2 、m3和m4 及脑干m1 表达较依赖组减少 ,MK80 1 (0 .1 2 5mg·kg- 1 )处理后脊髓m2 、m3和m5以及脑干m2 和m5表达增加 ,脊髓和脑干m1 和m4 表达减少 ;NOS抑制剂L NAME(1 0mg·kg- 1 )处理后脊髓和脑干m1 、m3、m5受体表达减少。结论 NMDA受体拮抗剂以及NOS抑制剂对M受体亚型基因调控是控制戒断症状的机制之一。

Objective To observe the effect of NMDA receptor antagonist or NOS inhibitor on muscarinic receptor subtype in rat spinal cord and brainstem during morphine withdrawal. Method The levels of muscarinic receptor subtype mRNA were determined by using RT PCR, the β actin mRNA expression was used as an internal control. Results The levels of m 1?m 2?m 3?m 4 and m 5 mRNA in spinal cord and m 1 and m 2 in brainstem were increased significantly during morphine dependence, and the levels of m 1?m 2?m 3 and m 4 in spinal cord and m 1 and m 5 in brainstem were decreased at 1 hour after the injection of naloxone (4.kg -1 , ip) in morphine dependent rats. MK801(0.125 .kg -1 ), NMDA receptor antagonist was administered (ip) at 30 min before the injection of naloxone in morphine dependent rats, the levels of m 2, m 3 and m 5 in spinal cord and m 2 and m 5 in brainstem were increased , and m 1and m 4 in both spinal cord and brainstem decreased. Pretreated with the L N nitroarginine methylester(10 .kg -1 ), a competitive inhibitor of NOS, the levels of m 1,m 3 and m 5 in spinal cord and m 1 ?m 4 and m 5 in brainstem decreased. Conclusion The data suggested that NMDA receptor and nitric oxide production may be involved in morphine dependence through the regulation of M receptor subtypes expression in spinal cord and brainstem.