Cited by 114Neurotransmitter Receptor Influence on BehaviorPI3K/AKT/mTOR signaling in cancerNeuroscience and Neuropharmacology Research

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

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Neasta, Jeremie, Barak, Segev, Hamida, Sami Ben, Ron, Dorit·2014·Journal of Neurochemistry

Abstract

The mammalian (or mechanistic) target of rapamycin (mTOR) complex 1 (mTORC 1) is a serine and threonine kinase that regulates cell growth, survival, and proliferation. mTORC 1 is a master controller of the translation of a subset of mRNA s. In the central nervous system mTORC 1 plays a crucial role in mechanisms underlying learning and memory by controlling synaptic protein synthesis. Here, we review recent evidence suggesting that the mTORC 1 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 mTORC 1 activation may alter brain functions. Finally, we propose that mTORC 1 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. image 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.

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  • mTORC1 plays a major role in molecular mechanisms of learning and memory and is involved in epilepsy, Parkinson's disease, Alzheimer's disease, and addiction.

    “As such, mTORC1 plays a major role in the molecular mechanisms associated with learning and memory147 and is involved in several brain disorders, including epilepsy, Parkinson’s disease, Alzheimer’s disease, and addiction.148,149”

    From Neurobiology of addiction: a neurocircuitry analysis (2016) · cites this paper as [149]

  • Exposure to drug and alcohol cues activates the mTORC1 pathway in the hippocampus, frontal cortex, nucleus accumbens, and amygdala.

    “Exposure to drug and alcohol cues activates the mTORC1 pathway in the hippocampus, frontal cortex, nucleus accumbens, and amygdala.149”

    From Neurobiology of addiction: a neurocircuitry analysis (2016) · cites this paper as [149]

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  1. Ron D Wang J The NMDA Receptor and Alcohol Addiction 2009 21204417

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Authors
Neasta, J., Barak, S., Hamida, S. B., & Ron, D.
Affiliations
  • Department of Neurology University of California San Francisco California USA
  • University of California, San Francisco (US)
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
2014-04-19
Volume
130
Issue
2
Pages
172-184
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
OpenAlex
W2048970463
Cited by
114
References
120
Citations by year
2026: 1 · 2025: 7 · 2024: 2 · 2023: 10 · 2022: 5 · 2021: 14 · 2020: 10 · 2019: 11 · 2018: 12 · 2017: 9 · 2016: 17 · 2015: 12 · 2014: 4
FWCI
1.60
Type
journal article
Language
en
Open access
Locations
  • Journal of Neurochemistry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
NIAAA (P50 AA012870)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
mTORC1, drug addiction, neural adaptation, drugs of abuse, synaptic protein synthesis, translational regulation, stimulants, cannabinoids, opiates, alcohol, reward seeking, relapse, limbic system, mTORC1 inhibitors, addiction treatment
MeSH terms
Mechanistic Target of Rapamycin Complex 1, Adaptation, Physiological, Animals, Autophagy, Behavior, Humans, Immunosuppressive Agents, Synaptic Transmission, Neurons, RNA, Messenger, Illicit Drugs, Protein Biosynthesis, Signal Transduction, Substance-Related Disorders, Sirolimus, Multiprotein Complexes, TOR Serine-Threonine Kinases

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