URB597 Prevents the Short-Term Excitotoxic Cell Damage in Rat Cortical Slices: Role of Cannabinoid 1 Receptors

Karla Chavira-Ramos, Mario Orozco-Morales, Çimen Karasu, Alexey A. Tinkov, Michael Aschner, Abel Santamaría, Ana Laura Colín-González

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Endocannabinoid-based therapies constitute an emerging tool for the potential treatment of neurodegenerative disorders, requiring characterization at the experimental level. The effects of URB597, an inhibitor of the fatty acid amide hydrolase (FAAH), were tested against the quinolinic acid (QUIN)-induced early toxic effects in rat cortical slices, and compared with those effects exerted by the endocannabinoid anandamide (AEA). URB597 prevented the QUIN-induced loss of mitochondrial function/cell viability and lipid peroxidation, while reduced necrosis, and to a lesser extent, apoptosis. The protective effects of URB597 were mediated by activation of cannabinoid receptor 1 (CB1r), as evidenced by their inhibition by the selective CB1r antagonist AM281. Similar effects were observed when testing AEA against QUIN toxicity. Our findings demonstrate the neuroprotective properties of URB597 during the early stages of excitotoxic damage to cortical tissue, suggesting that these properties are mediated by FAAH inhibition, and might be linked to the protective effects of AEA, or the combination of endocannabinoids.

Original languageEnglish (US)
Pages (from-to)146-155
Number of pages10
JournalNeurotoxicity Research
Volume39
Issue number2
DOIs
StatePublished - Apr 2021

Keywords

  • AM281
  • Anandamide
  • Endocannabinoid system
  • Excitotoxicity
  • Fatty acid amide hydrolase
  • URB597

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

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