Skip to main content

Daytime spikes in dopaminergic activity drive rapid mood-cycling in mice.

Publication ,  Journal Article
Sidor, MM; Spencer, SM; Dzirasa, K; Parekh, PK; Tye, KM; Warden, MR; Arey, RN; Enwright, JF; Jacobsen, JPR; Kumar, S; Remillard, EM; Caron, MG ...
Published in: Mol Psychiatry
November 2015

Disruptions in circadian rhythms and dopaminergic activity are involved in the pathophysiology of bipolar disorder, though their interaction remains unclear. Moreover, a lack of animal models that display spontaneous cycling between mood states has hindered our mechanistic understanding of mood switching. Here, we find that mice with a mutation in the circadian Clock gene (ClockΔ19) exhibit rapid mood-cycling, with a profound manic-like phenotype emerging during the day following a period of euthymia at night. Mood-cycling coincides with abnormal daytime spikes in ventral tegmental area (VTA) dopaminergic activity, tyrosine hydroxylase (TH) levels and dopamine synthesis. To determine the significance of daytime increases in VTA dopamine activity to manic behaviors, we developed a novel optogenetic stimulation paradigm that produces a sustained increase in dopamine neuronal activity and find that this induces a manic-like behavioral state. Time-dependent dampening of TH activity during the day reverses manic-related behaviors in ClockΔ19 mice. Finally, we show that CLOCK acts as a negative regulator of TH transcription, revealing a novel molecular mechanism underlying cyclic changes in mood-related behavior. Taken together, these studies have identified a mechanistic connection between circadian gene disruption and the precipitation of manic episodes in bipolar disorder.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Mol Psychiatry

DOI

EISSN

1476-5578

Publication Date

November 2015

Volume

20

Issue

11

Start / End Page

1406 / 1419

Location

England

Related Subject Headings

  • Ventral Tegmental Area
  • Tyrosine 3-Monooxygenase
  • Time Factors
  • Swimming
  • Rats
  • Psychiatry
  • Mutation
  • Motor Activity
  • Mice, Transgenic
  • Mice, Inbred C57BL
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Sidor, M. M., Spencer, S. M., Dzirasa, K., Parekh, P. K., Tye, K. M., Warden, M. R., … McClung, C. A. (2015). Daytime spikes in dopaminergic activity drive rapid mood-cycling in mice. Mol Psychiatry, 20(11), 1406–1419. https://doi.org/10.1038/mp.2014.167
Sidor, M. M., S. M. Spencer, K. Dzirasa, P. K. Parekh, K. M. Tye, M. R. Warden, R. N. Arey, et al. “Daytime spikes in dopaminergic activity drive rapid mood-cycling in mice.Mol Psychiatry 20, no. 11 (November 2015): 1406–19. https://doi.org/10.1038/mp.2014.167.
Sidor MM, Spencer SM, Dzirasa K, Parekh PK, Tye KM, Warden MR, et al. Daytime spikes in dopaminergic activity drive rapid mood-cycling in mice. Mol Psychiatry. 2015 Nov;20(11):1406–19.
Sidor, M. M., et al. “Daytime spikes in dopaminergic activity drive rapid mood-cycling in mice.Mol Psychiatry, vol. 20, no. 11, Nov. 2015, pp. 1406–19. Pubmed, doi:10.1038/mp.2014.167.
Sidor MM, Spencer SM, Dzirasa K, Parekh PK, Tye KM, Warden MR, Arey RN, Enwright JF, Jacobsen JPR, Kumar S, Remillard EM, Caron MG, Deisseroth K, McClung CA. Daytime spikes in dopaminergic activity drive rapid mood-cycling in mice. Mol Psychiatry. 2015 Nov;20(11):1406–1419.

Published In

Mol Psychiatry

DOI

EISSN

1476-5578

Publication Date

November 2015

Volume

20

Issue

11

Start / End Page

1406 / 1419

Location

England

Related Subject Headings

  • Ventral Tegmental Area
  • Tyrosine 3-Monooxygenase
  • Time Factors
  • Swimming
  • Rats
  • Psychiatry
  • Mutation
  • Motor Activity
  • Mice, Transgenic
  • Mice, Inbred C57BL