title: Administration of URB597, oleoylethanolamide or palmitoylethanolamide increases waking and dopamine in rats.
abstract: BACKGROUND
  Oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) are amides of fatty acids and ethanolamine named N-acylethanolamines or acylethanolamides. The hydrolysis of OEA and PEA is catalyzed by the fatty acid amide hydrolase (FAAH). A number of FAAH inhibitors that increase the levels of OEA and PEA in the brain have been developed, including URB597. In the present report, we examined whether URB597, OEA or PEA injected into wake-related brain areas, such as lateral hypothalamus (LH) or dorsal raphe nuclei (DRN) would promote wakefulness (W) in rats.
  
  
  RESULTS
  Male Wistar rats (250-300 g) were implanted for sleep studies with electrodes to record the electroencephalogram and electromyogram as well as a cannulae aimed either into LH or into DRN. Sleep stages were scored to determine W, slow wave sleep (SWS) and rapid eye movement sleep (REMS). Power spectra bands underly neurophysiological mechanisms of the sleep-wake cycle and provide information about quality rather than quantity of sleep, thus fast Fourier transformation analysis was collected after the pharmacological trials for alpha (for W; α = 8-12 Hz), delta (for SWS; δ = 0.5-4.0 Hz) and theta (for REMS; θ = 6.0-12.0 Hz). Finally, microdialysis samples were collected from a cannula placed into the nucleus accumbens (AcbC) and the levels of dopamine (DA) were determined by HPLC means after the injection of URB597, OEA or PEA. We found that microinjection of compounds (10, 20, 30 µg/1 µL; each) into LH or DRN during the lights-on period increased W and decreased SWS as well as REMS and enhanced DA extracellular levels.
  
  
  CONCLUSIONS
  URB597, OEA or PEA promoted waking and enhanced DA if injected into LH or DRN. The wake-promoting effects of these compounds could be linked with the enhancement in levels of DA and indirectly mediated by anandamide.
authors.affiliation: Laboratorio de Neurociencias Moleculares e Integrativas, Escuela de Medicina, División Ciencias de la Salud, Universidad Anáhuac Mayab, Mérida, Yucatán, México. eric.murillo@anahuac.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: Oscar
authors.initials: O
authors.lastname: Arias-Carrión
authors.forename: René
authors.initials: R
authors.lastname: Drucker-Colín
mesh_terms: D000577:Amides; D000581:Amidohydrolases / Q000037:antagonists & inhibitors; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D002219:Carbamates / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D063388:Endocannabinoids; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004983:Ethanolamines; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009829:Oleic Acids / Q000494:pharmacology*; D010169:Palmitic Acids / Q000494:pharmacology*; D051381:Rats; D012890:Sleep / Q000187:drug effects; D014851:Wakefulness / Q000187:drug effects*; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000577:Amides; D000581:Amidohydrolases; D001549:Benzamides; D002219:Carbamates; D004298:Dopamine; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D004983:Ethanolamines; D009829:Oleic Acids; D010169:Palmitic Acids; D000099252:Fatty Acid Amide Hydrolases; C500528:cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester; C488250:oleoylethanolamide; C005958:palmidrol