Differential role of anandamide and 2-arachidonoylglycerol in memory and anxiety-like responses

Arnau Busquets-Garcia, Emma Puighermanal, Antoni Pastor, Rafael De La Torre, Rafael Maldonado, Andrés Ozaita

Research output: Contribution to journalArticleResearchpeer-review

204 Citations (Scopus)


Background: Cannabinoid agonists are potential therapeutic agents because of their antinociceptive and anxiolytic-like effects, although an important caveat to their use is the possible adverse responses related to memory impairment. An alternative approach to circumvent this limitation consists of enhancing the concentration of the endocannabinoids anandamide and 2-arachidonoylglycerol. Methods: Using low doses of the specific inhibitors of the endocannabinoid metabolizing enzymes fatty acid amide hydrolase, URB597, and monoacylglycerol lipase, JZL184, we analyzed their acute and chronic effects on memory consolidation, anxiolytic-like effects, and nociception in mice (n = 612 per experimental group). Results: We show that anandamide is a central component in the modulation of memory consolidation, whereas 2-arachidonoylglycerol is not involved in this process. Interestingly, both URB597 and JZL184 induce anxiolytic-like effects through different cannabinoid receptors. In addition, the results show that the antinociceptive and anxiolytic-like responses of both inhibitors, as well as their acute effects on memory consolidation, are maintained after chronic treatment. Conclusions: These results dissociate the role of anandamide and 2-arachidonoylglycerol in memory consolidation and anxiety and reveal the interest of cannabinoid receptor 2 as a novel target for the treatment of anxiety-related disorders. © 2011 Society of Biological Psychiatry.
Original languageEnglish
Pages (from-to)479-486
JournalBiological Psychiatry
Issue number5
Publication statusPublished - 1 Sep 2011


  • Anxiety
  • cannabinoid receptor 2 (CB2)
  • endocannabinoid
  • memory
  • nociception
  • tolerance


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