Deletion of the GABAA receptor β3 subunit eliminates the hypnotic actions of oleamide in mice

Abstract

Oleamide (OA) is an endogenous unsaturated fatty acid amide with demonstrated sleep promoting effects in rodents. The sleep enhancing actions of OA may be mediated through interactions with the GABAergic, serotonergic or cannabinergic receptor systems. In this study, we investigated the possible interaction of OA with the GABA_A receptor by administering OA to mice with a targeted mutation of the GABA_A receptor β3 subunit (Gabarb3−/−). Peripherally administered OA significantly decreased sleep latency and wake time, while it increased non-rapid eye movement and total sleep times in wild-type (Gabarb3+/+) mice. OA failed to have any sleep-wake effect in Gabarb3−/− mice. On 24 h baseline recordings, no differences between Gabarb3−/− and Gabarb3+/+ mice were observed, indicating that the lack of a pharmacological response to OA in the Gabarb3−/− animals was not secondary to disruptions in physiological. sleep. Therefore, one mechanism by which OA exerts its sleep effects may be through interactions with GABA_A receptors containing the β3 subunit.