Candeletti Sanzio, Lopetuso Giuseppe, Cannarsa Rosalia, Cavina Chiara, Romualdi Patrizia
Department of Pharmacology, University of Bologna, Bologna, Italy.
J Mol Neurosci. 2006;30(3):341-7. doi: 10.1385/JMN:30:3:341.
A low abuse liability is reported for tramadol, an analgesic drug centrally acting through either opioid or nonopioid mechanisms. In this paper, we evaluated the effects of the repeated administration (7 d) of different doses of tramadol (10, 20, and 80 mg/kg, intraperitoneally) on the opioid precursor prodynorphin biosynthesis, in comparison with morphine (10 mg/kg, intraperitoneally), in the rat central nervous system (CNS). Northern analysis showed that morphine and tramadol produced different effects. While morphine caused a downregulation of prodynorphin mRNA levels in all investigated areas (hypothalamus, hippocampus, and striatum), tramadol did not cause any significant change in the striatum, and did not decrease prodynorphin biosynthesis in the hypothalamus and in the hippocampus, at nontoxic doses (10 and 20 mg/kg). The highest dose of tramadol (80 mg/kg) decreased prodynorphin mRNA levels in the hypothalamus and the hippocampus but not in the striatum. These data give some information on tramadol effects at molecular level in the CNS. They indicate that the alterations of prodynorphin gene expression caused by tramadol and morphine show a different pattern that may be related to the different abuse potential of the two analgesic drugs.
曲马多是一种通过阿片类或非阿片类机制发挥中枢作用的镇痛药，据报道其滥用可能性较低。在本文中，我们评估了不同剂量的曲马多（10、20和80毫克/千克，腹腔注射）重复给药（7天）对阿片类前体强啡肽生物合成的影响，并与吗啡（10毫克/千克，腹腔注射）在大鼠中枢神经系统（CNS）中的作用进行了比较。Northern分析表明，吗啡和曲马多产生了不同的作用。吗啡导致所有研究区域（下丘脑、海马体和纹状体）的强啡肽mRNA水平下调，而曲马多在无毒剂量（10和20毫克/千克）下，在纹状体中未引起任何显著变化，在下丘脑和海马体中也未降低强啡肽的生物合成。曲马多的最高剂量（80毫克/千克）降低了下丘脑和海马体中强啡肽mRNA的水平，但在纹状体中未降低。这些数据提供了关于曲马多在中枢神经系统分子水平作用的一些信息。它们表明，曲马多和吗啡引起的强啡肽基因表达改变呈现出不同的模式，这可能与这两种镇痛药不同的滥用潜力有关。
