Article (Scientific journals)
Mammalian target of rapamycin complex 1 and its downstream effector collapsin response mediator protein-2 drive reinstatement of alcohol reward seeking
Ben Hamida, S.; Laguesse, Sophie; Morisot, N. et al.
2018In Addiction Biology
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Keywords :
CRMP2; mTORC1; relapse; alcohol; conditioned place preference; translation
Abstract :
[en] 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, attenuates 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. © 2018 Society for the Study of Addiction.
Research center :
UCSF-Neurology Unite, Ron lab
Disciplines :
Neurology
Author, co-author :
Ben Hamida, S.;  Department of Neurology University of California San Francisco, CA USA, Douglas Research Center, McGill University, Montreal, Canada
Laguesse, Sophie  ;  Université de Liège - ULiège > Giga - Neurosciences
Morisot, N.;  Department of Neurology University of California San Francisco, CA USA, Brains On-line LLC, South San Francisco, CA, USA
Park, J.-H.;  Convergence Research Center for Diagnosis, Treatment and Care System of Dementia Korea Institute of Science and Technology (KIST) Republic of Korea, Division of Bio-Medical Science and Technology, KIST School Korea University of Science and Technology Republic of Korea
Phuamluong, K.;  Department of Neurology University of California San Francisco, CA USA
Berger, A. L.;  Department of Neurology University of California San Francisco, CA USA
Park, K. D.;  Convergence Research Center for Diagnosis, Treatment and Care System of Dementia Korea Institute of Science and Technology (KIST) Republic of Korea, Division of Bio-Medical Science and Technology, KIST School Korea University of Science and Technology Republic of Korea
Ron, D.;  Department of Neurology University of California San Francisco, CA USA
Language :
English
Title :
Mammalian target of rapamycin complex 1 and its downstream effector collapsin response mediator protein-2 drive reinstatement of alcohol reward seeking
Publication date :
2018
Journal title :
Addiction Biology
ISSN :
1355-6215
eISSN :
1369-1600
Publisher :
Blackwell Publishing Ltd
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 04 February 2019

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