AsianScientist (Aug. 17, 2017) – A research group in China has found that two proteins involved in the recycling of cellular components regulate cellular and behavioral responses to morphine. Their study was published in the journal Autophagy.
Drug addiction is a chronic and relapsing brain disorder characterized by compulsive drug use, sensitization and dependence. Because of the impact on health and social cohesion, drug addiction has become one of the biggest health problems across the world and caused an enormous financial burden on society. However, the exact mechanism underlying addiction has not been fully elucidated.
Autophagy is the process by which cells recycle their internal components. Previous studies have revealed that chronic morphine treatment can trigger autophagy, and co-administration of melatonin with morphine ameliorates morphine-induced behavioral sensitization and analgesic tolerance. But how autophagy contributes to the development of addictive behaviors has not been answered.
Both autophagy related 5 (ATG5) and autophagy related 7 (ATG7) are required for the maintenance of axonal homeostasis. Hence, the researchers hypothesized that autophagy contributes to morphological changes in neuronal dendritic cells and the resulting behavioral consequences from morphine exposure.
Using mouse animal models, the team led by Dr. Yao Yonggang and Dr. Xu Lin at the Kunming Institute of Zoology of the Chinese Academy of Sciences in collaboration with Dr. Ding Yuqiang at the Tongji University found that repeated morphine administration led to upregulation of ATG5 and ATG7 expression. This in turn facilitated the formation of the ATG12-ATG5 conjugate and resulted in Atg5- and Atg7-dependent autophagy in the dopaminergic neurons.
The detrimental effects of morphine-induced autophagy could be counteracted by a knocking out either ATG5 or ATG7 in dopaminergic neurons, protecting neuron function and preventing the development of addictive behaviors. Manipulation of autophagy might thus be explored as a potential therapeutic strategy in the future treatment of drug addiction, the researchers said.
The article can be found at: Su et al. (2017) Atg5- and Atg7-Dependent Autophagy in Dopaminergic Neurons Regulates Cellular and Behavioral Responses to Morphine.
———
Source: Chinese Academy of Sciences; Photo: Shutterstock.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.
