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On July 19th Autotophagy, a journal in the field of autophagy, published online a paper by the Kunming Institute of Zoology of the Chinese Academy of Sciences entitled Atg5-and Atg7-dependent autophagy in dopaminergic neurons regulates cellular and behavioral responses to morphine.
the study sheds light on the molecular mechanisms by which dopamine neuron-specific autophagy is involved in morphine addiction.
drug addiction, which plagues human health, is one of the major social problems, showing a chronic path of recurrent dependence, which is manifested as compulsory drug use, sensitivity and dependence, and its mechanism is still not clear.
currently, there is a lack of a fully effective way to treat drug addiction, and the rate of relapse after compulsory withdrawal is high.
therefore, it is very important to study the biological mechanism of addiction for the treatment and intervention of addiction.
morphine is a typical representative of opioids, and studying the mechanism of morphine addiction can provide new ideas and theoretical basis for clarifying the molecular mechanism and clinical treatment of opioid addiction.
autophagy is the process by which cells mediated by lysoes degrade their own organs and proteins, which is closely related to cell survival, cell differentiation, development and body stability.
studies have shown that autophagy abnormalities are associated with many diseases, including tumors, immunological diseases, and neurodegenerative diseases.
previous studies by researchers in the United States have shown that mitochondrial function is abnormal during morphine addiction, which in turn induces autophagy.
melatonin is an antioxidant that targets mitochondria and can interfere with this process.
Pre-treatment of cells and mice with melatonin can save morphine-induced mitochondrial dysfunction, thereby saving morphine-induced autophagy and ultimately blocking morphine-induced behavioral sensitivity and photohealth pain tolerance in mice (Feng et al.2013.Autophagy 9:1395-406).
but whether autophagy is involved in addiction, or whether it is a by-product of addiction, is not explained.
In order to verify the status of autophagy in morphine addiction, and to explain the molecular mechanism of morphine-induced autophagy, and to clarify the role of autophagy in the process of morphine addiction and analgesics, Yao Yonggang of Kunming Animal Institute and his co-researchers carried out systematic research from molecular, cellular and mouse animal models.
the model of morphine addiction in mice, first confirmed that morphine-induced autophagy is involved in addiction, not an addiction by-product.
Then, focusing on the molecular mechanisms of morphine-induced autophagy on primary neurons in mice, it was found that morphine causes significant increases in ATG5 and ATG7 protein expression, thereby promoting the formation of ATG12-ATG5 complexes in dopamine-energy neurons and the increased autophagy activity of Atg5 and Atg7 dependence.
further studies have found that autophagy, which relies on Atg5 and Atg7, regulates addiction behavior by regulating the descens density, descele complexity, and total descens length of dopamine neurons.
The specific knock-out of the Atg5 or Atg7 genes in dopamine-specific neurons significantly saves morphine-induced autophagy-induced descentic changes in dentum plasticity and ultimately blocks morphine-induced addictive behavior, including morphine reward effects, behavior sensitivity, pain tolerance, and withdrawal symptoms.
the results of this study elaborate the molecular mechanism of morphine-induced autophagy, which is expected to provide new ideas and scientific basis for the treatment of addiction and clinical analgesics.
, Ph.D. student at Kunming Animal Institute, co-authored the article, and researchers Yao Yonggang and Xu Lin were co-authors.
work was also helped by Ding Yuqiang, a professor at Tongji University.
the above-mentioned research has been funded by the National Natural Science Foundation of China, the Chinese Academy of Sciences brain function link map pilot special and the Chinese Academy of Sciences cutting-edge key research projects.
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