Mammalian target of rapamycin complex 1 and its downstream effector collapsin response mediator protein-2 drive reinstatement of alcohol reward seeking.
Mammalian target of rapamycin complex 1 and its downstream effector collapsin response mediator protein-2 drive reinstatement of alcohol reward seeking.
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雷帕霉素复合物1的哺乳动物靶标及其下游效应子折叠蛋白反应介质蛋白2驱动恢复酒精奖励的恢复。
DOI：
10.1111/adb.12653
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发表时间：
2019-09
影响因子：
3.4
通讯作者：
Ron D
中科院分区：
文献类型：
--
作者：
Ben Hamida S;Laguesse S;Morisot N;Park JH;Phuamluong K;Berger AL;Park KD;Ron D
Alcohol use disorder is a chronic relapsing disease. Maintaining abstinence represents a major challenge for alcohol- dependent patients. Yet the molecular underpinnings of alcohol relapse remain poorly understood. In the present study, we investigated the potential role of the mammalian target of rapamycin complex 1 (mTORC1) in relapse to alcohol-seeking behavior by using the reinstatement of a previously extinguished alcohol conditioned place preference (CPP) response as a surrogate relapse paradigm. We found that mTORC1 is activated in the nucleus accumbens shell following alcohol priming-induced reinstatement of alcohol place preference. We further report that the selective mTORC1 inhibitor, rapamycin, abolishes reinstatement of alcohol place preference. Activation of mTORC1 initiates the translation of synaptic proteins, and we observed that reinstatement of alcohol CPP is associated with increased protein levels of one of mTORC1’s downstream targets, collapsin response mediator protein-2 (CRMP2), in the nucleus accumbens. Importantly, the level of mTORC1 activation and CRMP2 expression positively correlate with the CPP score during reinstatement. Finally, we found that systemic administration of the CRMP2 inhibitor, lacosamide, atten- uates alcohol priming-induced reinstatement of CPP. Together, our results reveal that mTORC1 and its downstream target, CRMP2, contribute to mechanisms underlying reinstatement of alcohol reward seeking. Our results could have important implications for the treatment of relapse to alcohol use and position the Food and Drug Administration approved drugs, rapamycin and lacosamide, for the treatment of alcohol use disorder.
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影响因子：
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影响因子：
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Ron D
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11
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Liu, F.;Laguesse, S.;Legastelois, R.;Morisot, N.;Ben Hamida, S.;Ron, D.
通讯作者：
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影响因子：
3.4
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