Ozdogan Umit Kazim, Lähdesmäki Janne, Hakala Kristo, Scheinin Mika
Department of Pharmacology and Clinical Pharmacology, University of Turku, Itäinen Pitkäkatu 4, FI-20520 Turku, Finland.
Eur J Pharmacol. 2004 Aug 23;497(2):161-71. doi: 10.1016/j.ejphar.2004.06.051.
Alpha(2)-adrenoceptor agonists potentiate opioid analgesia and alleviate opioid withdrawal. The effects of two alpha(2)-adrenoceptor agonists, clonidine (2 mg/kg) and dexmedetomidine (20 and 100 microg/kg), and the alpha(1)-adrenoceptor antagonist prazosin (0.5 mg/kg) were tested on morphine analgesia, tolerance, and withdrawal in wild-type and alpha(2A)-adrenoceptor knock-out (KO) mice. Analgesia and tolerance were assessed with the tail-flick test. Withdrawal was precipitated with naloxone. Prazosin potentiated morphine analgesia equally in both genotypes. Clonidine and dexmedetomidine had no analgesic effects in alpha(2A)-adrenoceptor KO mice, but morphine analgesia and tolerance were similar in both genotypes. Alpha(2A)-Adrenoceptor KO mice exhibited 70% fewer naloxone-precipitated jumps than wild-type mice; weight loss was similar in both genotypes. The alpha(2)-adrenoceptor agonists reduced opioid withdrawal signs only in wild-type mice. We conclude that alpha(2A)-adrenoceptors are not directly involved in morphine analgesia and tolerance, and not critical for potentiation of morphine analgesia by prazosin, but that alpha(2A)-adrenoceptors modulate the expression of opioid withdrawal signs in mice.
α₂肾上腺素能受体激动剂可增强阿片类药物的镇痛作用并减轻阿片类药物戒断症状。在野生型和α₂A -肾上腺素能受体基因敲除（KO）小鼠中，测试了两种α₂肾上腺素能受体激动剂可乐定（2毫克/千克）和右美托咪定（20和100微克/千克）以及α₁肾上腺素能受体拮抗剂哌唑嗪（0.5毫克/千克）对吗啡镇痛、耐受性和戒断的影响。用甩尾试验评估镇痛和耐受性。用纳洛酮诱发戒断反应。哌唑嗪在两种基因型小鼠中均同等程度地增强吗啡镇痛作用。可乐定和右美托咪定在α₂A -肾上腺素能受体基因敲除小鼠中无镇痛作用，但两种基因型小鼠的吗啡镇痛和耐受性相似。α₂A -肾上腺素能受体基因敲除小鼠出现纳洛酮诱发的跳跃反应比野生型小鼠少70%；两种基因型小鼠的体重减轻情况相似。α₂肾上腺素能受体激动剂仅在野生型小鼠中减轻阿片类药物戒断症状。我们得出结论，α₂A -肾上腺素能受体不直接参与吗啡镇痛和耐受性，对哌唑嗪增强吗啡镇痛作用也不重要，但α₂A -肾上腺素能受体可调节小鼠阿片类药物戒断症状的表现。
