Jaw S P, Makimura M, Oh K W, Hoskins B, Ho I K
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216.
Eur J Pharmacol. 1994 May 12;257(1-2):153-60. doi: 10.1016/0014-2999(94)90707-2.
The dependence liability of a class of opioid agonist/antagonist analgesics, e.g. pentazocine, butorphanol, and buprenorphine, is widely recognized. However, the relative involvement of mu-, delta-, and kappa-opioid receptors mediating physical dependence on these compounds is not completely known. In the present study, butorphanol dependence was produced by continuous intracerebroventricular (i.c.v.) infusion of butorphanol (26 nmol/h) for 3 days in male Sprague-Dawley rats. Nor-binaltorphimine, a long-acting kappa-opioid receptor antagonist, and naloxone, a nonspecific antagonist, were administered i.c.v. to precipitate withdrawal in butorphanol-dependent animals, so as to investigate the involvement of central kappa-opioid receptors in opioid dependence. ED50 ratios (naloxone/nor-binaltorphimine) for eliciting withdrawal signs were: teeth-chattering (1.25), yawning (2.13), and ejaculation (0.72). Our data indicate that nor-binaltorphimine precipitated withdrawal behaviors similar to those precipitated by naloxone. It appears that central kappa-opioid receptors may play a major role in the development of butorphanol dependence in rats.
一类阿片类激动剂/拮抗剂镇痛药（如喷他佐辛、布托啡诺和丁丙诺啡）的依赖性已得到广泛认可。然而，介导对这些化合物产生身体依赖性的μ-、δ-和κ-阿片受体的相对参与情况尚不完全清楚。在本研究中，通过在雄性Sprague-Dawley大鼠中连续3天脑室内（i.c.v.）输注布托啡诺（26 nmol/h）来产生布托啡诺依赖性。长效κ-阿片受体拮抗剂诺美沙朵和非特异性拮抗剂纳洛酮通过脑室内给药，以促使布托啡诺依赖性动物出现戒断反应，从而研究中枢κ-阿片受体在阿片类药物依赖性中的作用。引发戒断症状的ED50比值（纳洛酮/诺美沙朵）分别为：打齿颤（1.25）、打哈欠（2.13）和射精（0.72）。我们的数据表明，诺美沙朵引发的戒断行为与纳洛酮引发的相似。看来中枢κ-阿片受体可能在大鼠布托啡诺依赖性的形成中起主要作用。
