title: Revealing the role of the endocannabinoid system modulators, SR141716A, URB597 and VDM-11, in sleep homeostasis.
abstract: The endocannabinoid system comprises receptors (CB1and CB2cannabinoid 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 CB1cannabinoid 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, 20mg/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 CB1cannabinoid receptor, FAAH and AMT, modulate the sleep homeostasis after prolonged waking.
authors.affiliation: Laboratorio de Neurociencias Moleculares e Integrativas, Escuela de Medicina División Ciencias de la Salud, Universidad Anáhuac Mayab, Mérida, Yucatán, Mexico; Grupo de Investigación en Envejecimiento, División Ciencias de la Salud Universidad Anáhuac Mayab, Mérida, Yucatán, Mexico; Intercontinental Neuroscience Research Group. Electronic address: eric.murillo@anahuac.mx.
authors.forename: Eric
authors.initials: E
authors.lastname: Murillo-Rodríguez
authors.affiliation: Intercontinental Neuroscience Research Group; Laboratory of Panic and Respiration, Institute of Psychiatry Federal University of Rio de Janeiro (IPUB/UFRJ), Rio de Janeiro, Brazil; Physical Activity Neuroscience Laboratory, Physical Activity Sciences Postgraduate Program-Salgado de Oliveira University (UNIVERSO), Niterói, Brazil.
authors.forename: Sergio
authors.initials: S
authors.lastname: Machado
authors.affiliation: Intercontinental Neuroscience Research Group; Health School, Polytechnic Institute of Porto, Porto, Portugal.
authors.forename: Nuno Barbosa
authors.initials: NB
authors.lastname: Rocha
authors.affiliation: Intercontinental Neuroscience Research Group; Faculty of Human Sciences, Medical School Hamburg, Hamburg, Germany; Physical Activity, Physical Education, Health and Sport Research Centre (PAPESH), Sports Science Department, School of Science and Engineering, Reykjavik University, Reykjavik, Iceland; Lithuanian Sports University, Kaunas, Lithuania.
authors.forename: Henning
authors.initials: H
authors.lastname: Budde
authors.affiliation: Intercontinental Neuroscience Research Group; School of Psychology, Nanjing Normal University Nanjing, China.
authors.forename: Ti-Fei
authors.initials: TF
authors.lastname: Yuan
authors.affiliation: Intercontinental Neuroscience Research Group; Unidad de Trastornos del Movimiento y Sueño (TMS) Hospital General "Dr. Manuel Gea González", Ciudad de México, Mexico.
authors.forename: Oscar
authors.initials: O
authors.lastname: Arias-Carrión
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D063385:Cannabinoid Receptor Modulators / Q000494:pharmacology*; D002219:Carbamates / Q000494:pharmacology*; D002408:Catheters, Indwelling; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids / Q000378:metabolism; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D017208:Rats, Wistar; D000077285:Rimonabant; D012890:Sleep / Q000187:drug effects* / Q000502:physiology; D012892:Sleep Deprivation / Q000188:drug therapy / Q000378:metabolism
chemical_list: D001095:Arachidonic Acids; D001549:Benzamides; D063385:Cannabinoid Receptor Modulators; D002219:Carbamates; D063388:Endocannabinoids; C462953:N-(2-methyl-3-hydroxyphenyl)-5,8,11,14-eicosatetraenamide; D010880:Piperidines; D011720:Pyrazoles; C500528:cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester; D000077285:Rimonabant
keywords: HPLC; REM sleep; alertness; microdialysis; serotonin; sleep deprivation