Antidepressant effects of sleep deprivation require astrocyte-dependent adenosine mediated signaling

Transl Psychiatry. 2013 Jan 15;3(1):e212. doi: 10.1038/tp.2012.136.


Major depressive disorder is a debilitating condition with a lifetime risk of ten percent. Most treatments take several weeks to achieve clinical efficacy, limiting the ability to bring instant relief needed in psychiatric emergencies. One intervention that rapidly alleviates depressive symptoms is sleep deprivation; however, its mechanism of action is unknown. Astrocytes regulate responses to sleep deprivation, raising the possibility that glial signaling mediates antidepressive-like actions of sleep deprivation. Here, we found that astrocytic signaling to adenosine (A1) receptors was required for the robust reduction of depressive-like behaviors following 12 hours of sleep deprivation. As sleep deprivation activates synaptic A1 receptors, we mimicked the effect of sleep deprivation on depression phenotypes by administration of the A1 agonist CCPA. These results provide the first mechanistic insight into how sleep deprivation impacts mood, and provide a novel pathway for rapid antidepressant development by modulation of glial signaling in the brain.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Analysis of Variance
  • Animals
  • Astrocytes / drug effects*
  • Astrocytes / physiology
  • Behavior, Animal
  • Depression / metabolism*
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Imipramine / pharmacology
  • Immunohistochemistry
  • Mice
  • Mice, Inbred C57BL
  • Purinergic P1 Receptor Agonists / metabolism
  • Purinergic P1 Receptor Agonists / pharmacology*
  • Receptor, Adenosine A1 / drug effects*
  • Receptor, Adenosine A1 / metabolism
  • SNARE Proteins / metabolism*
  • Sleep Deprivation / metabolism*
  • Sleep Stages


  • Purinergic P1 Receptor Agonists
  • Receptor, Adenosine A1
  • SNARE Proteins
  • Imipramine