Kaplan G B, Leite-Morris K A, Sears M T
Department of Psychiatry and Human Behavior, Brown University School of Medicine, Providence, RI 02908-4799.
Brain Res. 1994 Sep 19;657(1-2):347-50. doi: 10.1016/0006-8993(94)90990-3.
The possibility that central adenosine A1 and A2a receptors mediate opiate dependence was examined in morphine-treated mice using radioligand binding methods. Mice treated with morphine for 72 h demonstrated significant increases in naloxone precipitated abstinence behaviors of jumping, wet-dog shakes, teeth chattering, forepaw trends, forepaw tremors and diarrhea compared to vehicle-treated mice. Increased concentrations of cortical adenosine A1 receptor sites, but not striatal adenosine A2a sites, were found in saturation binding studies from morphine-dependent mice. Decreases in cortical A1 agonist binding affinity values along with increases in agonist binding sites were demonstrated in competition binding studies. These results suggest that adaptive changes of upregulation and sensitization of adenosine A1 receptors play a role in mediating the opiate abstinence syndrome.
利用放射性配体结合方法，在吗啡处理的小鼠中研究了中枢腺苷A1和A2a受体介导阿片类药物依赖的可能性。与溶剂处理的小鼠相比，用吗啡处理72小时的小鼠在纳洛酮诱发的戒断行为（如跳跃、湿狗样抖动、牙齿打颤、前爪趋势、前爪震颤和腹泻）方面表现出显著增加。在对吗啡依赖小鼠的饱和结合研究中发现，皮质腺苷A1受体位点浓度增加，但纹状体腺苷A2a位点浓度未增加。在竞争结合研究中，皮质A1激动剂结合亲和力值降低，同时激动剂结合位点增加。这些结果表明，腺苷A1受体上调和敏化的适应性变化在介导阿片类药物戒断综合征中起作用。
