Wang Xiaojia, Wang Yueqi, Xin Haoyang, Liu Yanyou, Wang Yuhui, Zheng Hang, Jiang Zhou, Wan Chaomin, Wang Zhengrong, Ding Jian M
West China Medical Center, Sichuan University, Chengdu, Sichuan 610041, China.
J Circadian Rhythms. 2006 Aug 22;4:9. doi: 10.1186/1740-3391-4-9.
Every physiological function in the human body exhibits some form of circadian rhythmicity. Under pathological conditions, however, circadian rhythmicity may be disrupted. Patients infected with HIV or addicted to drugs of abuse often suffer from sleep disorders and altered circadian rhythms. Early studies in Drosophila suggested that drug seeking behavior might be related to the expression of certain circadian clock genes. Our previous research showed that conditioned place preference with morphine treatment was altered in mice lacking the Period-1 (mPer1) circadian clock gene. Thus, we sought to investigate whether morphine treatment could alter the expression of mPer1, especially in brain regions outside the SCN and in peripheral tissues. Our results using Western blot analysis showed that the mPER1 immunoreactivity exhibited a strong circadian rhythm in the brains of the control (Con), morphine-dependent (MD), and morphine-withdrawal (MW) mice. However, the phase of the circadian rhythm of mPER1 expression in the brains of MD mice significantly differed from that of the Con mice (p < 0.05). In contrast to mPER1 expression in the brain, the circadian rhythm of mPER1 immunoreactivity in the kidneys was abolished after morphine administration, whereas the Con mice maintained robust circadian rhythmicity of mPER1 in the kidney. Therefore, the effect of morphine on the circadian clock gene mPer1 may vary among different organs, resulting in desynchronization of circadian function between the SCN and peripheral organs.
人体的每一项生理功能都呈现出某种形式的昼夜节律性。然而，在病理状态下，昼夜节律性可能会被打乱。感染HIV或滥用药物成瘾的患者常常患有睡眠障碍和昼夜节律改变。早期对果蝇的研究表明，觅药行为可能与某些生物钟基因的表达有关。我们之前的研究表明，在缺乏周期蛋白1（mPer1）生物钟基因的小鼠中，吗啡处理引起的条件性位置偏爱发生了改变。因此，我们试图研究吗啡处理是否会改变mPer1的表达，特别是在视交叉上核（SCN）以外的脑区和外周组织中。我们使用蛋白质免疫印迹分析的结果显示，在对照（Con）小鼠、吗啡依赖（MD）小鼠和吗啡戒断（MW）小鼠的大脑中，mPER1免疫反应性呈现出强烈的昼夜节律。然而，MD小鼠大脑中mPer1表达的昼夜节律相位与Con小鼠的显著不同（p < 0.05）。与大脑中mPer1的表达相反，吗啡给药后，肾脏中mPER1免疫反应性的昼夜节律消失，而Con小鼠的肾脏中mPer1保持强大的昼夜节律性。因此，吗啡对生物钟基因mPer1的影响可能因不同器官而异，导致SCN与外周器官之间的昼夜功能失调。
