title: Differential role of anandamide and 2-arachidonoylglycerol in memory and anxiety-like responses.
abstract: 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 = 6-12 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.
authors.affiliation: Facultat de Ciències de la Salut i de la Vida, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Arnau
authors.initials: A
authors.lastname: Busquets-Garcia
authors.forename: Emma
authors.initials: E
authors.lastname: Puighermanal
authors.forename: Antoni
authors.initials: A
authors.lastname: Pastor
authors.forename: Rafael
authors.initials: R
authors.lastname: de la Torre
authors.forename: Rafael
authors.initials: R
authors.lastname: Maldonado
authors.forename: Andrés
authors.initials: A
authors.lastname: Ozaita
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000378:metabolism / Q000502:physiology*; D001549:Benzamides / Q000494:pharmacology; D052117:Benzodioxoles / Q000494:pharmacology; D063387:Cannabinoid Receptor Antagonists; D002219:Carbamates / Q000494:pharmacology; D004361:Drug Tolerance; D063388:Endocannabinoids; D005989:Glycerides / Q000378:metabolism / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008994:Monoacylglycerol Lipases / Q000037:antagonists & inhibitors; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000378:metabolism; D043882:Receptors, Cannabinoid / Q000096:biosynthesis / Q000235:genetics; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D000700:Analgesics; D014151:Anti-Anxiety Agents; D001095:Arachidonic Acids; D001549:Benzamides; D052117:Benzodioxoles; D063387:Cannabinoid Receptor Antagonists; D002219:Carbamates; D063388:Endocannabinoids; D005989:Glycerides; D008994:Monoacylglycerol Lipases; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D058570:TOR Serine-Threonine Kinases; D000099252:Fatty Acid Amide Hydrolases; C534333:JZL 184; C500528:cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester; C094503:glyceryl 2-arachidonate; C546843:mTOR protein, mouse; C078814:anandamide