Cited by 48Circadian rhythm and melatoninNeurotransmitter Receptor Influence on BehaviorSirtuins and Resveratrol in Medicine

NAD+ cellular redox and SIRT1 regulate the diurnal rhythms of tyrosine hydroxylase and conditioned cocaine reward

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Logan, Ryan W., Parekh, Puja K., Kaplan, Gabrielle N., Becker-Krail, Darius D., Williams, Wilbur P., Yamaguchi, Shintaro, Yoshino, Jun, Shelton, Micah A. +9 more·2019·Molecular Psychiatry

Abstract

The diurnal regulation of dopamine is important for normal physiology and diseases such as addiction. Here we find a novel role for the CLOCK protein to antagonize CREB-mediated transcriptional activity at the tyrosine hydroxylase (TH) promoter, which is mediated by the interaction with the metabolic sensing protein, Sirtuin 1 (SIRT1). Additionally, we demonstrate that the transcriptional activity of TH is modulated by the cellular redox state, and daily rhythms of redox balance in the ventral tegmental area (VTA), along with TH transcription, are highly disrupted following chronic cocaine administration. Furthermore, CLOCK and SIRT1 are important for regulating cocaine reward and dopaminergic (DAergic) activity, with interesting differences depending on whether DAergic activity is in a heightened state and if there is a functional CLOCK protein. Taken together, we find that rhythms in cellular metabolism and circadian proteins work together to regulate dopamine synthesis and the reward value for drugs of abuse.

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Crossref · 10.1038/s41380-018-0061-1

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  • SIRT1 binds to CLOCK at the promoter of the gene encoding tyrosine hydroxylase in dopaminergic neurons to control rhythms in TH expression and dopamine synthesis.

    “SIRT1 binds to CLOCK at the promoter of the gene encoding tyrosine hydroxylase (TH) in dopaminergic neurons to control rhythms in TH expression and, ultimately, dopamine synthesis264”
  • Circadian genes in brain regions outside the SCN contribute locally to the control of neuronal metabolism, neurotransmitter synthesis and activity, and disruption of these functions might contribute to brain disorders.

    “circadian genes in other brain regions outside of this central pace-maker also contribute locally to the control of neuronal metabolism, neurotransmitter synthesis and activity, and the disruption of these functions might contribute to brain disorders264,304–315”
  • In the mouse ventral tegmental area, circadian regulation of SIRT1-dependent metabolic signalling is mechanistically linked to dopaminergic neurotransmission, which is important for drug reward.

    “This study demonstrates mechanistic links between circadian regulation of SIRT1-dependent metabolic signalling and dopaminergic neurotransmission in the mouse ventral tegmental area, which is important for drug reward.”

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Authors
Logan, R. W., Parekh, P. K., Kaplan, G. N., Becker-Krail, D. D., Williams, W. P., Yamaguchi, S., Yoshino, J., Shelton, M. A., Zhu, X., Zhang, H., Waplinger, S., Fitzgerald, E., Oliver-Smith, J., Sundarvelu, P., Enwright, J. F., Huang, Y. H., & McClung, C. A.
Affiliations
  • University of Pittsburgh (US)
  • Washington University in St. Louis (US)
Corresponding author
McClung, Colleen A.
Venue
Molecular Psychiatry
Published
2018-05-04
Volume
24
Issue
11
Pages
1668-1684
ISSN
  • 1359-4184 (ISSN-L)
  • 1476-5578
OpenAlex
W2802469003
Cited by
48
References
129
Citations by year
2026: 3 · 2025: 4 · 2024: 6 · 2023: 8 · 2022: 4 · 2021: 9 · 2020: 10 · 2019: 1 · 2018: 3
FWCI
3.24
Type
journal article
Language
en
Open access
Locations
  • Molecular Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Japan Society for the Promotion of Science (18K15399)
  • National Institute of Mental Health (R01MH106460, R01MH082876)
  • National Institute on Drug Abuse (R01DA023988, R33DA041872, R21DA041872, R21DA037636, R01DA039865, K02DA042886, K01DA038654)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK104995, P30DK056341)
  • National Institute of Neurological Disorders and Stroke (R21NS058339, T32NS086749)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
Keywords
NAD+, SIRT1, tyrosine hydroxylase, diurnal cycle, circadian clock, clock proteins, cellular redox state, cocaine reward, ventral tegmental area, dopamine synthesis, addiction, circadian metabolism
MeSH terms
Animals, Brain, Circadian Rhythm, Cocaine, Conditioning, Psychological, Conditioning, Operant, Male, Mice, Inbred BALB C, NAD, Neurons, Nucleus Accumbens, Oxidation-Reduction, Reward, Tyrosine 3-Monooxygenase, Ventral Tegmental Area, Mice, Sirtuin 1, CLOCK Proteins

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