Administration of URB597, Oleoylethanolamide or Palmitoylethanolamide Increases Waking and Dopamine in RatsReportar como inadecuado

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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.

Methodology and Principal Findings

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.


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.

Autor: Eric Murillo-Rodríguez , Marcela Palomero-Rivero, Diana Millán-Aldaco, Oscar Arias-Carrión, René Drucker-Colín



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