Diurnal variation of arachidonoylethanolamine, palmitoylethanolamide and oleoylethanolamide in the brain of the rat.

The diurnal variations of the endocannabinoid arachidonoylethanolamine (anandamide, ANA) as well as palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) were detected and quantified in cerebrospinal fluid (CSF), pons, hippocampus, and hypothalamus in the rat over 24 h using HPLC/MS. In CSF, the 3 compounds presented an increase in their concentration during the lights-on period and a remarkable decrease in their values during the lights-off period. In the pons, ANA, PEA and OEA showed the maximum values during the dark phase. On the other hand, we found that in the hippocampus, ANA increased its concentration during the lights-off period and PEA showed the highest peak at the beginning of the same period. OEA concentration showed no diurnal variations in the hippocampus. Finally, in the hypothalamus, ANA rose during the lights-on period whereas PEA and OEA presented the highest concentration at the end of the lights-off period. We postulate that all compounds are likely to be accumulated in parenchyma during the lights-off period (when animal is awake) and then, released into the CSF in order to reach target regions in turn to modulate diverse behaviors, such as feeding and sleep.