TY - JOUR
T1 - NAD+ cellular redox and SIRT1 regulate the diurnal rhythms of tyrosine hydroxylase and conditioned cocaine reward
AU - Logan, Ryan W.
AU - Parekh, Puja K.
AU - Kaplan, Gabrielle N.
AU - Becker-Krail, Darius D.
AU - Williams, Wilbur P.
AU - Yamaguchi, Shintaro
AU - Yoshino, Jun
AU - Shelton, Micah A.
AU - Zhu, Xiyu
AU - Zhang, Hui
AU - Waplinger, Spencer
AU - Fitzgerald, Ethan
AU - Oliver-Smith, Jeffrey
AU - Sundarvelu, Poornima
AU - Enwright, John F.
AU - Huang, Yanhua H.
AU - McClung, Colleen A.
N1 - Publisher Copyright:
© 2018, Macmillan Publishers Limited, part of Springer Nature.
PY - 2019/11/1
Y1 - 2019/11/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85046453337&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85046453337&partnerID=8YFLogxK
U2 - 10.1038/s41380-018-0061-1
DO - 10.1038/s41380-018-0061-1
M3 - Article
C2 - 29728703
AN - SCOPUS:85046453337
SN - 1359-4184
VL - 24
SP - 1668
EP - 1684
JO - Molecular Psychiatry
JF - Molecular Psychiatry
IS - 11
ER -
