Labuz D, Przewlocki R, Przewlocka B
Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Kraków, Poland.
Neurosci Lett. 2002 Dec 13;334(2):127-30. doi: 10.1016/s0304-3940(02)01121-7.
In the present study we investigated the development of tolerance to an antinociceptive effect after intrathecal administration of endomorphin-1, endomorphin-2 and morphine in tail-flick and paw pressure tests. We also assessed cross-tolerance between the antinociceptive effects of the two endogenous mu-opioid receptor agonists - endomorphins and morphine. The tolerance developed on day 3 after i.th. injection of both endomorphins, endomorphin-2 (18, 36 nmol), endomorphin-1 (16 nmol). After morphine (30 nmol) the tolerance developed on day 6. Our study described the cross-tolerance between morphine and endomorphin-1, but not endomorphin-2. In comparison with naive rats, morphine had a weaker antinociceptive effect in rats tolerant to endomorphin-1. In contrast, no cross-tolerance was observed after administration of endomorphin-2 in rats tolerant to endomorphin-1. In rats tolerant to endomorphin-2, the antinociceptive effect of morphine and endomorphin-1 was attenuated in both the tests used. Our results suggest that the three ligands of mu-opioid receptors probably act via different subtypes of the mu-opioid receptor.
在本研究中，我们通过甩尾和爪压痛试验，研究了鞘内注射内吗啡肽-1、内吗啡肽-2和吗啡后抗伤害感受作用耐受性的发展情况。我们还评估了两种内源性μ-阿片受体激动剂——内吗啡肽和吗啡的抗伤害感受作用之间的交叉耐受性。在鞘内注射两种内吗啡肽（内吗啡肽-2，18、36纳摩尔；内吗啡肽-1，16纳摩尔）后第3天产生耐受性。注射吗啡（30纳摩尔）后第6天产生耐受性。我们的研究描述了吗啡与内吗啡肽-1之间存在交叉耐受性，但与内吗啡肽-2之间不存在。与未处理的大鼠相比，吗啡对耐受内吗啡肽-1的大鼠的抗伤害感受作用较弱。相反，在耐受内吗啡肽-1的大鼠中注射内吗啡肽-2后未观察到交叉耐受性。在耐受内吗啡肽-2的大鼠中，吗啡和内吗啡肽-1在两种试验中的抗伤害感受作用均减弱。我们的结果表明，μ-阿片受体的这三种配体可能通过μ-阿片受体的不同亚型发挥作用。
