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http://hdl.handle.net/10397/90861
Title: | An autophagy-related protein Becn2 regulates cocaine reward behaviors in the dopaminergic system | Authors: | Kim, YJ Kong, Q Yamamoto, S Kuramoto, K Huang, M Wang, N Hwa, J Xiao, T Levine, B Qiu, X Zhao, Y Miller, RJ Dong, H Meltzer, HY Xu, M He, C |
Issue Date: | Feb-2021 | Source: | Science advances, 17 Feb. 2021, v. 7, no. 8, eabc8310 | Abstract: | Drug abuse is a foremost public health problem. Cocaine is a widely abused drug worldwide that produces various reward-related behaviors. The mechanisms that underlie cocaine-induced disorders are unresolved, and effective treatments are lacking. Here, we found that an autophagy-related protein Becn2 is a previously unidentified regulator of cocaine reward behaviors. Becn2 deletion protects mice from cocaine-stimulated locomotion and reward behaviors, as well as cocaine-induced dopamine accumulation and signaling, by increasing presynaptic dopamine receptor 2 (D2R) autoreceptors in dopamine neurons. Becn2 regulates D2R endolysosomal trafficking, degradation, and cocaine-induced behaviors via interacting with a D2R-bound adaptor GASP1. Inactivating Becn2 by upstream autophagy inhibitors stabilizes striatal presynaptic D2R, reduces dopamine release and signaling, and prevents cocaine reward in normal mice. Thus, the autophagy protein Becn2 is essential for cocaine psychomotor stimulation and reward through regulating dopamine neurotransmission, and targeting Becn2 by autophagy inhibitors is a potential strategy to prevent cocaine-induced behaviors. Copyright | Publisher: | American Association for the Advancement of Science (AAAS) | Journal: | Science advances | ISSN: | 2375-2548 | DOI: | 10.1126/sciadv.abc8310 | Rights: | © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. The following publication Kim, Y. J., Kong, Q., Yamamoto, S., Kuramoto, K., Huang, M., Wang, N., ... & He, C. (2021). An autophagy-related protein Becn2 regulates cocaine reward behaviors in the dopaminergic system. Science Advances, 7(8), eabc8310 is available at https://doi.org/10.1126/sciadv.abc8310 |
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