title: Inhibition of diacylglycerol lipase (DAGL) in the lateral hypothalamus of rats prevents the increase in REMS and food ingestion induced by PAR1 stimulation.
abstract: Stimulation of the protease-activated receptor 1 (PAR1) in vitro, was shown to induce synaptic retrograde signaling through the endocannabinoid 2-arachidonoylglycerol (2-AG) synthesis and activation of the cannabinoid receptor type 1 (CB1R). The activation of PAR1 by the agonist S1820 in the lateral hypothalamus (LH) increases rapid eye movement sleep (REMS) and food intake in rats, and both effects are prevented by the CB1R inverse agonist AM251. In the present study, we implanted rats with electrodes and with cannulae aimed bilaterally to the LH. We administered tetrahydrolipstatin (THL), an inhibitor of the diacylglycerol lipase (DAGL), the enzyme responsible for 2-AG synthesis, to evaluate the sleep-wake cycle and food ingestion. THL in the LH readily prevented the increase in REMS and food intake induced by PAR1 stimulation, further supporting 2-AG as an upstream activator of PAR1. Our results demonstrate that the effect of PAR1 on REMS and food intake is blocked by the inhibition of DAGL, further suggesting that PAR1 stimulation in the lateral hypothalamus of rats induces an increase in sleep and food intake through 2-AG.
authors.affiliation: Grupo de Neurociencias, Laboratorio de Canabinoides, Facultad de Medicina, Universidad Nacional Autónoma de México, México, D.F., México.
authors.forename: Marcel
authors.initials: M
authors.lastname: Pérez-Morales
authors.affiliation: División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México, D.F., México.
authors.forename: Ana María
authors.initials: AM
authors.lastname: López-Colomé
authors.affiliation: Grupo de Neurociencias, Laboratorio de Canabinoides, Facultad de Medicina, Universidad Nacional Autónoma de México, México, D.F., México.
authors.forename: Mónica
authors.initials: M
authors.lastname: Méndez-Díaz
authors.affiliation: Laboratorio de Neurogenómica Cognitiva, Coordinación de Psicofisiología, Facultad de Psicología, Universidad Nacional Autónoma deMéxico, México, D.F., México.
authors.forename: Alejandra E
authors.initials: AE
authors.lastname: Ruiz-Contreras
authors.affiliation: Grupo de Neurociencias, Laboratorio de Canabinoides, Facultad de Medicina, Universidad Nacional Autónoma de México, México, D.F., México. Electronic address: opg@unam.mx.
authors.forename: Oscar
authors.initials: O
authors.lastname: Prospéro-García
mesh_terms: D000818:Animals; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007026:Hypothalamic Area, Lateral / Q000201:enzymology*; D007783:Lactones / Q000494:pharmacology; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D000077403:Orlistat; D051381:Rats; D017208:Rats, Wistar; D044463:Receptor, PAR-1 / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology*
chemical_list: D004791:Enzyme Inhibitors; D007783:Lactones; D044463:Receptor, PAR-1; D000077403:Orlistat; D008071:Lipoprotein Lipase
keywords: 2-Arachidonoylglycerol; Cannabinoid receptor type 1; Food intake; Protease-activated receptor 1; Rapid eye movement sleep; Tetrahydrolipstatin