Forensic Department, Xi'an Jiaotong University School of Medicine, 76# West Yanta Road, Xi'an 710061, PR China.
Brain Res. 2012 Jan 18;1433:80-4. doi: 10.1016/j.brainres.2011.11.045. Epub 2011 Dec 2.
Repeated administration of opioids such as morphine leads to the development of tolerance to their pain-relieving effects as well as to physical dependence. Although the association between the dopamine system and the molecular mechanisms of morphine-induced antinociceptive tolerance has been studied, the possible interaction between morphine-induced tolerance and D3 receptors has not been investigated. In the present study, male mice lacking the dopamine D3 receptor gene were used to investigate the function of D3 receptors in the development of morphine-induced tolerance and withdrawal. Compared with wild-type (WT) mice, the dopamine D3 receptor knockout (D3R KO) mice showed pronounced hypoalgesia. The D3R KO mice clearly developed lower morphine-induced tolerance and showed attenuated withdrawal signs compared with the WT mice. These results suggest that D3 receptors regulate basal nociception and are involved in the development of morphine-induced tolerance and withdrawal.
反复给予吗啡等阿片类药物会导致其止痛效果产生耐受性，以及身体依赖性。虽然多巴胺系统与吗啡引起的镇痛耐受的分子机制之间的关系已经被研究过，但吗啡诱导的耐受与 D3 受体之间的可能相互作用尚未被研究。在本研究中，使用缺乏多巴胺 D3 受体基因的雄性小鼠来研究 D3 受体在吗啡诱导的耐受和戒断发展中的功能。与野生型（WT）小鼠相比，多巴胺 D3 受体敲除（D3R KO）小鼠表现出明显的痛觉减退。与 WT 小鼠相比，D3R KO 小鼠明显表现出较低的吗啡诱导的耐受，并且戒断症状减弱。这些结果表明 D3 受体调节基础痛觉，并参与吗啡诱导的耐受和戒断的发展。
