Development of antinociceptive tolerance and physical dependence following morphine i.c.v. infusion in mice.

Development of antinociceptive tolerance and physical dependence following morphine i.c.v. infusion in mice.
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注射吗啡后出现抗伤害耐受性和身体依赖性

DOI:
10.1016/j.ejphar.2005.10.031
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发表时间:
2005
期刊:
European journal of pharmacology.
影响因子:
--
通讯作者:
Roerig,SandraC
Roerig,SandraC
中科院分区:
--
文献类型:
--
作者:
Lenard,NatalieR;Roerig,SandraC

文献摘要

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已报告大鼠长期i. c. v.输注吗啡,但未报告小鼠。在本报告中,对i. c. v.吗啡输注和s.c.比较吗啡丸粒在小鼠中的植入。还评价了静脉注射吗啡后的身体依赖性。将渗透微型泵填充吗啡(50 mM),连接至i. c. v.插管,并皮下植入。以50 nmol/h递送3天(即,3.6μmol总量)。纳洛酮(1 mg/kg,s.c.)表明身体依赖性的发展。耐受i. c. v.,i.t.,和静脉注射吗啡(分别为6.3、2.0和4.4倍)。将小鼠植入含有75 mg吗啡的小球3天(即,10 ~ 260 μmol)对吗啡的耐受性分别为6.5、7.5和18倍。因此,使用两种方法产生的耐受性不相同。这些结果允许比较通过3种不同途径(i. c. v.,i.t.,和静脉注射)在通过两种途径(i. c. v.和s.c.)在一项研究中。
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 μmol 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., ∼260 μmol 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.