Anandamide may mediate sleep induction

Mechoulam, Raphael; Fride, Ester; Hanu, Lumir; Sheskin, Tzviel; Bisogno, Tiziana; Marzo, Vincenzo Di; Bayewitch, Michael; Vogel, Zvi

doi:10.1038/37891

Cited by 160 publications

(99 citation statements)

References 2 publications

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“…We cannot answer this question yet, but it might be likely that VDM-11 induces sleep via anandamide since it has been described that VDM-11 promotes the endogenous accumulation of this endocannabinoid (de Lago et al, 2004(de Lago et al, , 2005. In line with this idea, several pieces of evidence supports that anandamide promotes sleep (Mechoulam et al, 1997;Murillo-Rodrı´guez et al, 1998, 2011Herrera-Solis et al, 2010;Rueda-Orozco et al, 2010). Taken together, our data suggest that blocking AMT does not interfere with sleep rebound.…”

Section: Discussionsupporting

confidence: 67%

Revealing the role of the endocannabinoid system modulators, SR141716A, URB597 and VDM-11, in sleep homeostasis

et al. 2016

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Abstract-The endocannabinoid system comprises receptors (CB 1 and CB 2 cannabinoid receptors), enzymes (Fatty Acid Amide Hydrolase [FAAH], which synthesizes the endocannabinoid anandamide), as well as the anandamide membrane transporter (AMT). Importantly, previous experiments have demonstrated that the endocannabinoid system modulates multiple neurobiological functions, including sleep. For instance, SR141716A (the CB 1 cannabinoid receptor antagonist) as well as URB597 (the FAAH inhibitor) increase waking in rats whereas VDM-11 (the blocker of the AMT) enhances sleep in rodents. However, no further evidence is available regarding the neurobiological role of the endocannabinoid system in the homeostatic control of sleep. Therefore, the aim of the current experiment was to test if SR141716A, URB597 or VDM-11 would modulate the sleep rebound after sleep deprivation. Thus, these compounds were systemically injected (5, 10, 20 mg/kg; ip; separately each one) into rats after prolonged waking. We found that SR141716A and URB597 blocked in dose-dependent fashion the sleep rebound whereas animals treated with VDM-11 displayed sleep rebound during the recovery period. Complementary, injection after sleep deprivation of either SR141716A or URB597 enhanced dose-dependently the extracellular levels of dopamine (DA), norepinephrine (NE), epinephrine (EP), serotonin (5-HT), as well as adenosine (AD) while VDM-11 caused a decline in contents of these molecules. These findings suggest that SR141716A or URB597 behave as a potent stimulants since they suppressed the sleep recovery period after prolonged waking. It can be concluded that elements of the endocannabinoid system, such as the CB 1 cannabinoid receptor, FAAH and AMT, modulate the sleep homeostasis after prolonged waking. Ó

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Section: Discussionsupporting

confidence: 67%

Revealing the role of the endocannabinoid system modulators, SR141716A, URB597 and VDM-11, in sleep homeostasis

et al. 2016

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“…Oleamide accumu-ENDOCANNABINOID SYSTEM AND DISEASE lates in the cerebrospinal fluid of sleep-deprived cats (Cravatt et al, 1995) and rats and induces sleep, an effect which could be blocked by SR141716 . Initially, it was suggested that inhibition of anandamide degradation by FAAH rather than the activation of CB 1 receptors was responsible for the sleep-inducing effect of oleamide (Boring et al, 1996;Mechoulam et al, 1997), but this is a matter of dispute (Fowler, 2004;Lees and Dougalis, 2004;Leggett et al, 2004).…”

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confidence: 99%

The Endocannabinoid System as an Emerging Target of Pharmacotherapy

2006

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“…El 2-araquidonilglicerol es un agonista para los receptores CB1 y CB2, y tiene una mayor afinidad que la de anandamida para los receptores CB1 9,17 . La oleamida, que es una amida de ácido oléico, tiene efectos similares a la anandamida sobre los receptores CB1 18,19 .…”

Section: Endocanabinoides (Eicosanoides)unclassified