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Review
. 2014 Jul;130(2):172-84.
doi: 10.1111/jnc.12725. Epub 2014 Apr 19.

mTOR complex 1: a key player in neuroadaptations induced by drugs of abuse

Jeremie Neasta  1 , Segev Barak, Sami Ben Hamida, Dorit Ron
Affiliations
Review

mTOR complex 1: a key player in neuroadaptations induced by drugs of abuse

Jeremie Neasta et al. J Neurochem. 2014 Jul.

Abstract

The mammalian (or mechanistic) target of rapamycin (mTOR) complex 1 (mTORC1) is a serine and threonine kinase that regulates cell growth, survival, and proliferation. mTORC1 is a master controller of the translation of a subset of mRNAs. In the central nervous system mTORC1 plays a crucial role in mechanisms underlying learning and memory by controlling synaptic protein synthesis. Here, we review recent evidence suggesting that the mTORC1 signaling pathway promotes neuroadaptations following exposure to a diverse group of drugs of abuse including stimulants, cannabinoids, opiates, and alcohol. We further describe potential molecular mechanisms by which drug-induced mTORC1 activation may alter brain functions. Finally, we propose that mTORC1 is a focal point shared by drugs of abuse to mediate drug-related behaviors such as reward seeking and excessive drug intake, and offer future directions to decipher the contribution of the kinase to mechanisms underlying addiction. Recent studies suggesting that exposure to diverse classes of drugs of abuse as well as exposure to drug-associated memories lead to mTORC1 kinase activation in the limbic system. In turn, mTORC1 controls the onset and the maintenance of pathological neuroadaptions that underlie several features of drug addiction such as drug seeking and relapse. Therefore, we propose that targeting mTORC1 and its effectors is a promising strategy to treat drug disorders.

Keywords: addiction; alcohol; drugs of abuse; limbic system; mTOR; translation.

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Figures

Figure 1
Figure 1
A graphical model depicting the signaling cascades that are known to activate mTORC1 in response to exposure to drugs of abuse and a possible mechanism by which mTORC1 serves as a central player in drugs of abuse-dependent neuroadaptations that underlie phenotypes of drug addiction such as drug seeking and relapse.
See this image and copyright information in PMC

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