Kitto Kelley F, Fairbanks Carolyn A
Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA.
Eur J Pharmacol. 2006 Apr 24;536(1-2):133-7. doi: 10.1016/j.ejphar.2006.01.053. Epub 2006 Mar 20.
We have determined the effect of intracerebroventricularly (i.c.v.) administered decarboxylated arginine (agmatine) on supraspinally induced chronic morphine analgesic tolerance. Mice pre-treated with a schedule of chronic i.c.v administration of morphine (10 nmol, b.i.d. 3 days) show a 12-fold reduction in the potency of acutely administered i.c.v morphine compared to saline injected controls. Co-administration of agmatine (10 nmol) with one of the two daily morphine injections completely prevents the reduction in i.c.v morphine analgesia. Mice injected with agmatine once daily (but no morphine) do not show a increase in morphine analgesic potency relative to saline controls, indicating that a mere potentiation of acute morphine analgesia cannot account for the agmatine-mediated anti-tolerance effect in those mice subjected to the morphine tolerance induction schedule. These observations agree with previous reports that systemically and intrathecally administered agmatine prevent opioid tolerance, and extend these results to include a supraspinal site of action.
我们已经确定了脑室内注射脱羧精氨酸（胍丁胺）对脊髓上诱导的慢性吗啡镇痛耐受性的影响。预先经慢性脑室内注射吗啡（10纳摩尔，每日两次，共3天）处理的小鼠，与注射生理盐水的对照组相比，急性脑室内注射吗啡的效力降低了12倍。胍丁胺（10纳摩尔）与每日两次吗啡注射中的一次同时给药，可完全防止脑室内注射吗啡镇痛作用的降低。每天注射一次胍丁胺（但不注射吗啡）的小鼠，相对于生理盐水对照组，吗啡镇痛效力并未增加，这表明单纯增强急性吗啡镇痛作用并不能解释胍丁胺对接受吗啡耐受性诱导方案的小鼠的抗耐受性作用。这些观察结果与之前关于全身和鞘内注射胍丁胺可预防阿片类药物耐受性的报道一致，并将这些结果扩展到包括脊髓上作用部位。
