Brain region-specific changes in N-acylethanolamine contents with time of day

J Neurochem. 2014 Feb;128(4):491-506. doi: 10.1111/jnc.12495. Epub 2013 Nov 13.


The N-acylethanolamines (NAEs) exert important behavioral, physiological, and immunological effects through actions at cannabinoid and other receptors. We measured concentrations of three NAEs, the Km and Vmax for fatty acid amide hydrolysis (FAAH), FAAH protein and FAAH mRNA in prefrontal cortex, hippocampus, hypothalamus, amygdala, striatum, and cerebellum at 4 h intervals, starting at 03:00. Significant differences in N-arachidonylethanolamine contents among the times examined occur in the prefrontal cortex (PFC), hippocampus, hypothalamus, and striatum. N-Oleoylethanolamine concentrations exhibit large fluctuations over the day in the cerebellum, including a threefold decrease between 19:00 and 23:00. N-Palmitoylethanolamine and N-oleoylethanolamine were significantly, positively correlated in all regions examined except the hypothalamus. FAAH Km values are significantly affected by time of day in PFC, hippocampus and amygdala and FAAH Vmax values are significantly affected in PFC, hippocampus and cerebellum. However, correlational data indicate that FAAH does not play a primary role in the circadian regulation of the NAE concentrations. FAAH protein expression is not significantly different among the harvest times in any brain region examined. Concentrations of 2-arachidonoylglycerol are significantly affected by time of harvest in the striatum and cerebellum, but not in other brain regions. Together, these data indicate that the NAEs exhibit diverse patterns of change with time of day that are likely the result of alterations in biosynthesis, and support the hypothesis that N-arachidonylethanolamine is a tonic activator of cannabinoid receptor signaling.

Keywords: 2-arachidonoylglycerol; N-arachidonylethanolamine; N-oleoylethanolamine; circadian; fatty acid amide hydrolase; palmitoylethanolamide.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amidohydrolases / metabolism
  • Animals
  • Blotting, Western
  • Brain Chemistry / physiology*
  • Circadian Rhythm / physiology*
  • Data Interpretation, Statistical
  • Ethanolamines / metabolism*
  • Lipid Metabolism / physiology
  • Male
  • Mice
  • Mice, Inbred ICR
  • Phosphatidylethanolamines / metabolism
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Receptor, Cannabinoid, CB1 / metabolism


  • Ethanolamines
  • N-acylethanolamines
  • N-arachidonylphosphatidylethanolamine
  • Phosphatidylethanolamines
  • RNA, Messenger
  • Receptor, Cannabinoid, CB1
  • Amidohydrolases
  • fatty-acid amide hydrolase