µ-Opioid Receptors Expressed by Intrinsically Photosensitive Retinal Ganglion Cells Contribute to Morphine-Induced Behavioral Sensitization.
µ-Opioid Receptors Expressed by Intrinsically Photosensitive Retinal Ganglion Cells Contribute to Morphine-Induced Behavioral Sensitization.
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DOI：
10.3390/ijms232415870
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发表时间：
2022-12-14
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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阿片类药物是治疗中度至重度疼痛的最有效工具。尽管它们具有镇痛功效，但长期使用阿片类药物可导致药物耐受性，成瘾和睡眠/觉醒障碍。虽然阿片类药物和睡眠/觉醒问题之间的联系已经有了很好的记录，但阿片类药物相关的睡眠/觉醒问题的潜在机制在很大程度上仍未得到解决。重要的是，内在光敏视网膜神经节细胞（ipRGC），将环境光/暗信息传递到大脑的睡眠/昼夜节律中心以调节睡眠/觉醒行为的细胞，表达μ-阿片受体（MOR）。在这项研究中，我们探讨了ipRGC对阿片类药物相关睡眠/昼夜节律中断的潜在贡献。使用植入的遥测发射器，我们测量了水平运动活动和体温的变化，在小鼠的过程中的慢性吗啡范例。与具有正常莫尔表达模式的对照同窝仔相比，缺乏由ipRGC表达的MOR的小鼠（McKO）表现出减少的吗啡诱导的行为激活/致敏。相比之下，缺乏MORs的小鼠（MKO）没有获得吗啡诱导的运动激活/敏化。对照组小鼠在光照和黑暗阶段也表现出吗啡诱导的体温过低，而McKO同窝小鼠仅在黑暗中表现出吗啡诱导的体温过低。有趣的是，只有对照组的动物似乎对吗啡的低温效应产生了耐受性。然而，吗啡并没有急剧降低MKO小鼠的体温。这些发现支持了ipRGC表达的MORs可能导致阿片类药物相关的睡眠/觉醒问题和体温调节变化的观点。
Opioid drugs are the most effective tools for treating moderate to severe pain. Despite their analgesic efficacy, long-term opioid use can lead to drug tolerance, addiction, and sleep/wake disturbances. While the link between opioids and sleep/wake problems is well-documented, the mechanism underlying opioid-related sleep/wake problems remains largely unresolved. Importantly, intrinsically photosensitive retinal ganglion cells (ipRGCs), the cells that transmit environmental light/dark information to the brain’s sleep/circadian centers to regulate sleep/wake behavior, express μ-opioid receptors (MORs). In this study, we explored the potential contribution of ipRGCs to opioid-related sleep/circadian disruptions. Using implanted telemetry transmitters, we measured changes in horizontal locomotor activity and body temperature in mice over the course of a chronic morphine paradigm. Mice lacking MORs expressed by ipRGCs (McKO) exhibited reduced morphine-induced behavioral activation/sensitization compared with control littermates with normal patterns of MOR expression. Contrastingly, mice lacking MORs globally (MKO) did not acquire morphine-induced locomotor activation/sensitization. Control mice also showed morphine-induced hypothermia in both the light and dark phases, while McKO littermates only exhibited morphine-induced hypothermia in the dark. Interestingly, only control animals appeared to acquire tolerance to morphine’s hypothermic effect. Morphine, however, did not acutely decrease the body temperature of MKO mice. These findings support the idea that MORs expressed by ipRGCs could contribute to opioid-related sleep/wake problems and thermoregulatory changes.
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影响因子：
5.6
作者：
Cleymaet AM;Berezin CT;Vigh J
通讯作者：
Vigh J
影响因子：
4.3
作者：
Bergum, Nikolas;Berezin, Casey-Tyler;Vigh, Jozsef
通讯作者：
Vigh, Jozsef
DOI：
10.3390/ph15050527
发表时间：
2022-04-25
期刊：
Pharmaceuticals (Basel, Switzerland)
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.2
作者：
Chen, XH;Geller, EB;Adler, MW
通讯作者：
Adler, MW
影响因子：
2.9
作者：
Byku, M;Gannon, RL
通讯作者：
Gannon, RL