The hypnotic actions of oleamide are blocked by a cannabinoid receptor antagonist.
The unsaturated fatty acid amide oleamide (OA), which accumulates in the CSF of rats during sleep deprivation, induces electroencephalographically measured sleep when administered intracerebroventricularly. The mechanism of sleep induction by OA is unclear but may derive from enhancements of GABA or 5-HT receptor function, or alternatively from changes in the catabolism or uptake of the related fatty acid amide anandamide, an endogenous cannabinoid-1 (CB1) receptor ligand. The present study tests the latter hypothesis by administering OA alone and in combination with the CB1 receptor antagonist SR141716. As previously reported, 2.8 microg OA administered intracerebroventricularly significantly shortened electroencephalographic sleep latency. SR141716 in a dose of 3 microg had no effects on sleep by itself, but when co-administered with OA prevented its sleep-inducing effects. These data suggest that at least one aspect of the hypnotic action of OA involves interactions with the CB1 receptor system, possibly by blocking the metabolism of the endogenous CB1 receptor agonist anandamide.
Mendelson
W B
WB
Department of Psychiatry, The University of Chicago, IL 60637, USA.
Basile
A S
AS
D000818:Animals; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D008297:Male; D009829:Oleic Acids / Q000494:pharmacology* / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors*; D000077285:Rimonabant; D012890:Sleep / Q000187:drug effects* / Q000502:physiology*
D006993:Hypnotics and Sedatives; D009829:Oleic Acids; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C029407:oleylamide; D000077285:Rimonabant