Lenard Natalie R, Roerig Sandra C
Louisiana State University Health Sciences Center-Shreveport, Department of Pharmacology, Toxicology, and Neuroscience, USA.
Eur J Pharmacol. 2005 Dec 19;527(1-3):71-6. doi: 10.1016/j.ejphar.2005.10.031. Epub 2005 Nov 28.
The chronic i.c.v. infusion of morphine has been reported for rats but not for mice. In the current report, the antinociceptive tolerance to both i.c.v. morphine infusion and s.c. implantation of morphine pellets in mice was compared. Physical dependence after i.c.v. morphine infusion was also evaluated. Osmotic minipumps were filled with morphine (50 mM), connected to i.c.v. cannulae, and implanted s.c. to deliver 50 nmol/h for 3 days (i.e., 3.6 micromol total). Robust jumping precipitated by naloxone (1 mg/kg, s.c.) indicated the development of physical dependence. Tolerance to i.c.v., i.t., and i.v. morphine (6.3-, 2.0-, and 4.4-fold, respectively) was observed using the tail flick test. Mice implanted with pellets containing 75 mg morphine for 3 days (i.e., approximately 260 micromol total) were also tolerant to morphine (6.5-, 7.5- and 18-fold, respectively). Thus, the tolerance developed using the two methods was not identical. These results allow comparison of morphine tested by 3 different routes (i.c.v., i.t., and i.v.) after chronic morphine treatment by two routes (i.c.v. and s.c.) in a single study.
已有报道对大鼠进行慢性脑室内注射吗啡，但未对小鼠进行过此类研究。在本报告中，比较了小鼠对脑室内注射吗啡和皮下植入吗啡丸剂的抗伤害感受耐受性。还评估了脑室内注射吗啡后的身体依赖性。将渗透微型泵填充吗啡（50 mM），连接到脑室内插管，并皮下植入以每小时输送50 nmol，持续3天（即总量为3.6微摩尔）。纳洛酮（1 mg/kg，皮下注射）引发的强烈跳跃表明身体依赖性的发展。使用甩尾试验观察到对脑室内、鞘内和静脉注射吗啡的耐受性（分别为6.3倍、2.0倍和4.4倍）。植入含75 mg吗啡丸剂3天的小鼠（即总量约为260微摩尔）对吗啡也有耐受性（分别为6.5倍、7.5倍和18倍）。因此，使用这两种方法产生的耐受性并不相同。这些结果使得在一项研究中能够比较通过两种途径（脑室内和皮下）进行慢性吗啡治疗后，经三种不同途径（脑室内、鞘内和静脉注射）测试的吗啡。
