title: Fatty acid amide hydrolase (FAAH) inhibition enhances memory acquisition through activation of PPAR-alpha nuclear receptors.
abstract: Inhibitors of fatty acid amide hydrolase (FAAH) increase endogenous levels of anandamide (a cannabinoid CB(1)-receptor ligand) and oleoylethanolamide and palmitoylethanolamide (OEA and PEA, ligands for alpha-type peroxisome proliferator-activated nuclear receptors, PPAR-alpha) when and where they are naturally released in the brain. Using a passive-avoidance task in rats, we found that memory acquisition was enhanced by the FAAH inhibitor URB597 or by the PPAR-alpha agonist WY14643, and these enhancements were blocked by the PPAR-alpha antagonist MK886. These findings demonstrate novel mechanisms for memory enhancement by activation of PPAR-alpha, either directly by administering a PPAR-alpha agonist or indirectly by administering a FAAH inhibitor.
authors.affiliation: Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch, Intramural Research Program, NIDA, NIH, DHHS, Baltimore, Maryland 21224, USA.
authors.forename: Carmen
authors.initials: C
authors.lastname: Mazzola
authors.forename: Julie
authors.initials: J
authors.lastname: Medalie
authors.forename: Maria
authors.initials: M
authors.lastname: Scherma
authors.forename: Leigh V
authors.initials: LV
authors.lastname: Panlilio
authors.forename: Marcello
authors.initials: M
authors.lastname: Solinas
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Tanda
authors.forename: Filippo
authors.initials: F
authors.lastname: Drago
authors.forename: Jean Lud
authors.initials: JL
authors.lastname: Cadet
authors.forename: Steven R
authors.initials: SR
authors.lastname: Goldberg
authors.forename: Sevil
authors.initials: S
authors.lastname: Yasar
mesh_terms: D000581:Amidohydrolases / Q000037:antagonists & inhibitors*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D002219:Carbamates / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007858:Learning / Q000502:physiology*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D047493:PPAR alpha / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D001549:Benzamides; D002219:Carbamates; D004791:Enzyme Inhibitors; D047493:PPAR alpha; D011743:Pyrimidines; D018160:Receptors, Cytoplasmic and Nuclear; D000099252:Fatty Acid Amide Hydrolases; C500528:cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester; C006253:pirinixic acid