N-甲基-D-天冬氨酸受体拮抗剂氯胺酮抑制大鼠吗啡戒断症状的表达  

Suppression of morphine withdrawal signs by low doses of ketamine, a N-methyl-D-aspartate receptor antagonist

作　　者：冀栋[1] 隋滋野[1] 崔彩莲[1] 罗非[1] 韩济生[1] 

机构地区：[1]北京大学神经科学研究所,北京100083

出　　处：《北京大学学报（医学版）》2002年第4期326-332,共7页Journal of Peking University:Health Sciences

基　　金：科技部基础研究重大项目前期研究专项基金 (国科基字 [2 0 0 1] 5 0号 )资助~~

摘　　要：目的 :观察N 甲基 D 天冬氨酸 (N methyl D aspartate ,NMDA)受体拮抗剂氯胺酮 (ketamine)在不影响运动功能的条件下 ,是否能抑制吗啡依赖大鼠的戒断症状。方法 :给大鼠连续注射递增剂量吗啡 5d ,造成其对吗啡的依赖 ,用纳洛酮催促戒断症状的出现。应用行为药理学的研究方法 ,经腹腔 (2～ 16mg·kg-1)、侧脑室 (4～ 10 0μg)及相关核团 (0 .4～ 10 μg)给予不同剂量的氯胺酮。结果 :反复 4次 (1)腹腔注射 8mg·kg-1,最后一次注射 3h后 ,能显著抑制 2种戒断症状 ;16mg·kg-1能显著抑制 3种戒断症状。 (2 )反复 4次脑室注射 10 0 μg氯胺酮 ,能显著抑制 2种戒断症状。 (3)伏核内注入 0 .4～ 10 μg的氯胺酮可显著抑制 4种戒断症状 ,但注入杏仁核则无效。 结论 :在不影响大鼠运动功能的条件下 ,氯胺酮对吗啡戒断症状有明显抑制作用 。Objective: To elucidate whether ketamine, a non-competitive antagonist of the N-methyl-D-aspartate(NMDA) receptor, could suppress the withdrawal signs of morphine when it has no effect on the motor functions in rats. Methods: Rats were made dependent on morphine by multiple injections of morphine for 5 days. They were then given repeated intraperitoneal (i.p.) injections (2-16 mg·kg -1), or intracerebroventricular (i.c.v.) injections (4-100 μg), or intra-nucleus accumbens(NAc) and intra-amygdala microinjections (0.4-10 μg) of ketamine respectively, followed by i.p. administration of naloxone (1 mg·kg -1), and the withdrawal signs were scored for 30 min. Results: (1) 2/ 4 or 3/4 of the precipitated withdrawal signs were decreased by repeated i.p. 8 or 16 mg·kg -1 of ketamine 3 h after last administration; (2) 2/4 of the withdrawal signs were decreased by repeated i.c.v. 100 μg of ketamine; and (3) 4/4 of the withdrawal signs were decreased by repeated microinjections (0.4-10 μg) of ketamine to NAc, but not to amygdala. Conclusion: These results indicate that lower doses of ketamine are capable of suppressing morphine withdrawal signs in rats, and NAc could be the critical CNS site of the effect.

关 键 词：N-甲基-D-天冬氨酸受体拮抗剂 氯胺酮 大鼠 吗啡戒断症状 

分 类 号：R749.61[医药卫生—神经病学与精神病学]