Molecular Mechanism Regulating 24-Hour Rhythm of Dopamine D3 Receptor Expression in Mouse Ventral Striatum

Feb 23, 2013Molecular pharmacology

Molecular control of daily dopamine D3 receptor levels in the mouse reward system

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Abstract

The expression of the dopamine D3 receptor (DRD3) varies significantly over a 24-hour period.

  • Molecular components of the circadian clock regulate the daily variation in DRD3 expression.
  • Transcription of DRD3 is enhanced by the protein RORα and inhibited by REV-ERBα.
  • Downregulation or overexpression of REV-ERBα disrupts the oscillation of DRD3 expression in cells.
  • Binding of REV-ERBα to the DRD3 promoter increases during the early dark phase.
  • DRD3 protein levels are higher during the dark phase, influencing locomotor activity.
  • RORα and REV-ERBα operate in a feedback mechanism to modulate DRD3 expression throughout the day.

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Full Text

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