Caffeine prevents sleep loss-induced deficits in long-term potentiation and related signaling molecules in the dentate gyrus

Eur J Neurosci. 2010 Apr;31(8):1368-76. doi: 10.1111/j.1460-9568.2010.07175.x. Epub 2010 Apr 9.


We have previously reported that caffeine prevented sleep deprivation-induced impairment of long-term potentiation (LTP) of area CA1 as well as hippocampus-dependent learning and memory performance in the radial arm water maze. In this report we examined the impact of long-term (4-week) caffeine consumption (0.3 g/L in drinking water) on synaptic plasticity (Alhaider et al., 2010) deficit in the dentate gyrus (DG) area of acutely sleep-deprived rats. The sleep deprivation and caffeine/sleep deprivation groups were sleep-deprived for 24 h by using the columns-in-water technique. We tested the effect of caffeine and/or sleep deprivation on LTP and measured the basal levels as well as stimulated levels of LTP-related molecules in the DG. The results showed that chronic caffeine administration prevented the impairment of early-phase LTP (E-LTP) in the DG of sleep-deprived rats. Additionally, chronic caffeine treatment prevented the sleep deprivation-associated decreases in the basal levels of the phosphorylated calcium/calmodulin-dependent protein kinase II (P-CaMKII) and brain derived neurotrophic factor (BDNF) as well as in the stimulated levels of P-CaMKII in the DG area. The results suggest that chronic use of caffeine prevented anomalous changes in the basal levels of P-CaMKII and BDNF associated with sleep deprivation and as a result contributes to the revival of LTP in the DG region.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism
  • Caffeine / administration & dosage
  • Caffeine / pharmacology*
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Central Nervous System Stimulants / administration & dosage
  • Central Nervous System Stimulants / pharmacology*
  • Dentate Gyrus / drug effects*
  • Dentate Gyrus / physiopathology
  • In Vitro Techniques
  • Long-Term Potentiation / drug effects*
  • Male
  • Phosphorylation
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Sleep Deprivation / drug therapy*
  • Sleep Deprivation / physiopathology
  • Synapses / drug effects
  • Synapses / physiology
  • Time Factors


  • Brain-Derived Neurotrophic Factor
  • Central Nervous System Stimulants
  • Caffeine
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2