The administration of endocannabinoid uptake inhibitors OMDM-2 or VDM-11 promotes sleep and decreases extracellular levels of dopamine in rats

Eric Murillo-Rodríguez, Marcela Palomero-Rivero, Diana Millán-Aldaco, Vincenzo Di Marzo

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

The family of the endocannabinoid system comprises endogenous lipids (such as anandamide [ANA]), receptors (CB1/CB2 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 CB1 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 30μM; 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.

Original languageEnglish
Pages (from-to)88-95
Number of pages8
JournalPhysiology and Behavior
Volume109
Issue number1
DOIs
StatePublished - 17 Jan 2013

Keywords

  • Anandamide membrane transporter
  • Dopamine
  • Nucleus accumbens
  • Rapid eye movement sleep
  • Wakefulness

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