Upregulation of gene expression in reward-modulatory striatal opioid systems by sleep loss

Neuropsychopharmacology. 2013 Dec;38(13):2578-87. doi: 10.1038/npp.2013.174. Epub 2013 Jul 18.


Epidemiological studies have shown a link between sleep loss and the obesity 'epidemic,' and several observations indicate that sleep curtailment engenders positive energy balance via increased palatable-food 'snacking.' These effects suggest alterations in reward-modulatory brain systems. We explored the effects of 10 days of sleep deprivation in rats on the expression of striatal opioid peptide (OP) genes that subserve food motivation and hedonic reward, and compared effects with those seen in hypothalamic energy balance-regulatory systems. Sleep-deprived (Sleep-Dep) rats were compared with yoked forced-locomotion apparatus controls (App-Controls), food-restricted rats (Food-Restrict), and unmanipulated controls (Home-Cage). Detection of mRNA levels with in situ hybridization revealed a subregion-specific upregulation of striatal preproenkephalin and prodynorhin gene expression in the Sleep-Dep group relative to all other groups. Neuropeptide Y (NPY) gene expression in the hippocampal dentate gyrus and throughout neocortex was also robustly upregulated selectively in the Sleep-Dep group. In contrast, parallel gene expression changes were observed in the Sleep-Dep and Food-Restrict groups in hypothalamic energy-sensing systems (arcuate nucleus NPY was upregulated, and cocaine- and amphetamine-regulated transcript was downregulated), in alignment with leptin suppression in both groups. Together, these results reveal a novel set of sleep deprivation-induced transcriptional changes in reward-modulatory peptide systems, which are dissociable from the energy-balance perturbations of sleep loss or the potentially stressful effects of the forced-locomotion procedure. The recruitment of telencephalic food-reward systems may provide a feeding drive highly resistant to feedback control, which could engender obesity through the enhancement of palatable feeding.

Publication types

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

MeSH terms

  • Animals
  • Body Weight
  • Eating
  • Enkephalins / genetics
  • Enkephalins / metabolism
  • Fasting / physiology
  • Insulin / blood
  • Leptin / blood
  • Male
  • Neostriatum / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neuroimaging
  • Neuropeptide Y / genetics
  • Neuropeptide Y / metabolism
  • Opioid Peptides / genetics
  • Opioid Peptides / metabolism*
  • Protein Precursors / genetics
  • Protein Precursors / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reward*
  • Sleep Deprivation / pathology*
  • Up-Regulation / physiology*


  • Enkephalins
  • Insulin
  • Leptin
  • Nerve Tissue Proteins
  • Neuropeptide Y
  • Opioid Peptides
  • Protein Precursors
  • cocaine- and amphetamine-regulated transcript protein
  • proenkephalin
  • preproenkephalin