The hypnotic actions of the fatty acid amide, oleamide

Abstract

Oleamide is an endogenous fatty acid amide which can be synthesized de novo in the mammalian nervous system, and has been detected in human plasma. It accumulates in the CSF of rats after six hours of sleep deprivation and induces sleep in naive rats and mice. Inhibition of the primary catabolic enzyme of oleamide (fatty acid amide hydrolase) by trifluoromethyl-octadecenone reduces sleep latency and increases total sleep time when given centrally to rats and peripherally to mice. While the mechanism of action of oleamide is unclear, it has been demonstrated to increase the amplitude of currents gated by 5-HT2a, 5HT2c and GABAa receptors. Moreover, the action of oleamide most relevant to sleep induction involves, in part, cannabinergic pathways, as evidenced by the ability of the cannabinoid antagonist SR 141716 to inhibit the hypnotic actions of OA. Nonetheless, enhancement of cannabinergic function may not be the only mechanism by which OA alters sleep, as it can act synergistically with subthreshold doses of triazolam (0.125 microg) to reduce sleep latency. These findings raise the possibility that OA may be representative of a group of compounds which might be developed into clinically-used hypnotics, and are discussed in the context of fatty acid derivatives as modulators of neuronal function.