title: The administration of endocannabinoid uptake inhibitors OMDM-2 or VDM-11 promotes sleep and decreases extracellular levels of dopamine in rats.
abstract: The family of the endocannabinoid system comprises endogenous lipids (such as anandamide [ANA]), receptors (CB(1)/CB(2) cannabinoid receptors), metabolic enzymes (fatty acid amide hydrolase [FAAH]) and a putative membrane transporter (anandamide membrane transporter [AMT]). Although the role of ANA, FAAH or the CB(1) cannabinoid receptor in sleep modulation has been reported, the effects of the inhibition of AMT on sleep remain unclear. In the present study, we show that microdialysis perfusion in rats of AMT inhibitors, (9Z)-N-[1-((R)-4-hydroxbenzyl)-2-hydroxyethyl]-9-octadecenamide (OMDM-2) or N-(4-hydroxy-2-methylphenyl)-5Z,8Z,11Z,14Z-eicosatetraenamide (VDM-11; 10, 20 or 30 μM; each compound) delivered into the paraventricular thalamic nucleus (PVA) increased sleep and decreased waking. In addition, the infusion of compounds reduced the extracellular levels of dopamine collected from nucleus accumbens. Taken together, these findings illustrate a critical role of AMT in sleep modulation.
authors.affiliation: Laboratorio de Neurociencias Moleculares e Integrativas, Escuela de Medicina, División Ciencias de la Salud. Universidad Anáhuac Mayab, Mérida, Yucatán, Mexico. eric.murillo@ahanuac.mx
authors.forename: Eric
authors.initials: E
authors.lastname: Murillo-Rodríguez
authors.forename: Marcela
authors.initials: M
authors.lastname: Palomero-Rivero
authors.forename: Diana
authors.initials: D
authors.lastname: Millán-Aldaco
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001095:Arachidonic Acids / Q000008:administration & dosage*; D001593:Benzyl Compounds / Q000008:administration & dosage*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids / Q000378:metabolism; D045604:Extracellular Fluid / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D020644:Midline Thalamic Nuclei / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012890:Sleep / Q000187:drug effects*; D013997:Time Factors
chemical_list: D001095:Arachidonic Acids; D001593:Benzyl Compounds; D063388:Endocannabinoids; C462953:N-(2-methyl-3-hydroxyphenyl)-5,8,11,14-eicosatetraenamide; C474343:OMDM-2 cpd; D004298:Dopamine