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PNAS 106 (19): 8027-8031

Copyright © 2009 by the National Academy of Sciences.


Fat-induced satiety factor oleoylethanolamide enhances memory consolidation

Patrizia Campolongoa,b,c,1, Benno Roozendaalb,2, Viviana Trezzac,3, Vincenzo Cuomoc, Giuseppe Astaritaa, Jin Fua, James L. McGaughb, and Daniele Piomellia,d,4

aDepartment of Pharmacology, University of California, Irvine, CA 92697-4625; bDepartment of Neurobiology and Behavior and Center for the Neurobiology of Learning and Memory, University of California, Irvine, CA 92657-3800; cDepartment of Physiology and Pharmacology, University of Rome ‘La Sapienza’, Piazzale Aldo Moro 5, 00185 Roma, Italy; and dDrug Discovery and Development, Italian Institute of Technology, Via Morego 30, 16163 Genoa, Italy

Contributed by James L. McGaugh, March 19, 2009

Received for publication March 2, 2009.

Abstract: The ability to remember contexts associated with aversive and rewarding experiences provides a clear adaptive advantage to animals foraging in the wild. The present experiments investigated whether hormonal signals released during feeding might enhance memory of recently experienced contextual information. Oleoylethanolamide (OEA) is an endogenous lipid mediator that is released when dietary fat enters the small intestine. OEA mediates fat-induced satiety by engaging type-{alpha} peroxisome proliferator-activated receptors (PPAR-{alpha}) in the gut and recruiting local afferents of the vagus nerve. Here we show that post-training administration of OEA in rats improves retention in the inhibitory avoidance and Morris water maze tasks. These effects are blocked by infusions of lidocaine into the nucleus tractus solitarii (NTS) and by propranolol infused into the basolateral complex of the amygdala (BLA). These findings suggest that the memory-enhancing signal generated by OEA activates the brain via afferent autonomic fibers and stimulates noradrenergic transmission in the BLA. The actions of OEA are mimicked by PPAR-{alpha} agonists and abolished in mutant mice lacking PPAR-{alpha}. The results indicate that OEA, acting as a PPAR-{alpha} agonist, facilitates memory consolidation through noradrenergic activation of the BLA, a mechanism that is also critically involved in memory enhancement induced by emotional arousal.

Key Words: fatty acid ethanolamide • lipid • PPAR-{alpha}

Author contributions: P.C., B.R., V.C., J.L.M., and D.P. designed research; P.C., V.T., and J.F. performed research; G.A. contributed new reagents/analytic tools; P.C., J.L.M., and D.P. analyzed data; and P.C. and D.P. wrote the paper.

1Present address: Department of Physiology and Pharmacology, University of Rome ‘La Sapienza’, Piazzale Aldo Moro 5, 00185 Roma, Italy.

2Present address: Department of Neuroscience, Section of Anatomy, University Medical Center Groningen, 9713 AV, Groningen, The Netherlands.

3Present address: Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.

The authors declare no conflict of interest.

This article contains supporting information online at

4To whom correspondence should be addressed. E-mail: piomelli{at}

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