BAM8-22对吗啡耐受的影响

采用缩足反射观察椎管内注射感觉神经元特异性受体(SNSR)激动剂牛肾上腺髓质8-22肽(BAM8-22)对吗啡耐受的影响.结果表明,椎管内注射BAM8-22(0.1nmol)后,吗啡抗伤害作用的半数有效剂量由耐受时的80.99μg恢复至12.38μg(P<0.001);隔天混合给予BAM8-22后,能显著延缓吗啡耐受,第6天吗啡抗伤害作用的半数有效剂量为14.84μg,与吗啡耐受组相比有极显著差异(P<0.001);但这两组动物吗啡的抗伤害作用没有达到正常吗啡组水平(P<0.05和P<0.01).连续椎管内单独注射BAM8-22 6d后,吗啡抗伤害作用的半数有效剂量为12.23μg,明显高于正常吗啡组(P<0.01),但又明显低于吗啡耐受组(P<0.001).而椎管内连续6d混合给予BAM8-22和吗啡,并不能阻止吗啡耐受.研究表明,椎管内注射BAM8-22能部分翻转或延缓吗啡的耐受,而BAM8-22的长期作用则会部分降低吗啡的抗伤害作用,提示感觉神经元特异性受体参与了阿片受体功能的调制.

Effect of Bovine Adrenal Medulla 8-22 on Morphine Tolerance in Rats

To investigate the effect of intrathecal(i.t.) administration of bovine adrenal medulla 8-22(BAM8-22),an agonist of sensory neuron-specific receptors(SNSR),on morphine tolerance by paw withdrawal test.It was found that i.t.administration of BAM8-22(0.1 nmol) evidently reversed established morphine tolerance,half effective dose of morphine antinociception reduced from 80.99 μg in morphine tolerance to 12.38 μg after BAM8-22 reversed(P<0.001).Co-administration of BAM8-22(0.1 nmol) every other day,but not daily,with morphine remarkably attenuated the development of morphine tolerance,half effective dose of morphine antinociception in sixth day was 14.84 μg(P<0.001).But antinociception of these two groups didn’t reach to morphine in naive group level(P<0.05 and P<0.01).Half effective dose of morphine antinociception was 12.23 μg after i.t.administration of BAM8-22(0.1 nmol) daily for six days,it was significantly higher than morphine in naive group(P<0.05),but evidently lower than morphine tolerant group(P<0.001).Co-administration of BAM8-22 daily,with morphine didn’t attenuate the development of morphine to lerance.The present study showed that BAM8-22 inhibited the development and expression of tolerance to morphine,while chronic BAM8-22 weakened antinociceptive response of morphine.These results suggest that SNSR is involved in the modulation of opioid receptors function.