Deletion of the GABA(A) receptor beta 3 subunit eliminates the hypnotic actions of oleamide in mice.
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 GABAA receptor beta 3 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 beta 3 subunit.
Laposky
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Center for Sleep and Circadian Biology, Northwestern University, Hogan Hall Room 2-160, 2153 North Campus Drive, Evanston, IL 60208, USA.
Homanics
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Basile
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Mendelson
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D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D005260:Female; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016296:Mutagenesis / Q000502:physiology; D009829:Oleic Acids / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000235:genetics*; D012894:Sleep Stages / Q000187:drug effects* / Q000502:physiology*; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology
D006993:Hypnotics and Sedatives; D009829:Oleic Acids; D011963:Receptors, GABA-A; C029407:oleylamide