title: Modulation of fear memory by dietary polyunsaturated fatty acids via cannabinoid receptors.
abstract: Although the underlying mechanism remains unknown, several studies have suggested benefits of n-3 long-chain polyunsaturated fatty acid (PUFA) for patients with anxiety disorders. Elevated fear is thought to contribute to the pathogenesis of particular anxiety disorders. The aim of the present study was to evaluate whether the dietary n-3 to n-6 PUFA (3:6) ratio influences fear memory. For this purpose, the effects of various dietary 3:6 ratios on fear memory were examined in mice using contextual fear conditioning, and the effects of these diets on central synaptic transmission were examined to elucidate the mechanism of action of PUFA. We found that fear memory correlated negatively with dietary, serum, and brain 3:6 ratios in mice. The low fear memory in mice fed a high 3:6 ratio diet was increased by the cannabinoid CB1 receptor antagonist rimonabant, reaching a level seen in mice fed a low 3:6 ratio diet. The agonist sensitivity of CB1 receptor was enhanced in the basolateral nucleus of the amygdala (BLA) of mice fed a high 3:6 ratio diet, compared with that of mice fed a low 3:6 ratio diet. Similar enhancement was induced by pharmacological expulsion of cholesterol in the neuronal membrane of brain slices from mice fed a low 3:6 ratio diet. CB1 receptor-mediated short-term synaptic plasticity was facilitated in pyramidal neurons of the BLA in mice fed a high 3:6 ratio diet. These results suggest that the ratio of n-3 to n-6 PUFA is a factor regulating fear memory via cannabinoid CB1 receptors.
authors: 1] Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan [2] CREST, Japan Science and Technology Agency, Kawaguchi, Saitama, Japan.
authors: Daisuke
authors: D
authors: Yamada
authors: Central Research Laboratory, Tokyo Innovation Center, Nippon Suisan Kaisha, Hachioji, Tokyo, Japan.
authors: Jiro
authors: J
authors: Takeo
authors: 1] Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan [2] CREST, Japan Science and Technology Agency, Kawaguchi, Saitama, Japan [3] Medical University of Vienna, Vienna, Austria.
authors: Peter
authors: P
authors: Koppensteiner
authors: 1] Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan [2] CREST, Japan Science and Technology Agency, Kawaguchi, Saitama, Japan.
authors: Keiji
authors: K
authors: Wada
authors: 1] Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan [2] CREST, Japan Science and Technology Agency, Kawaguchi, Saitama, Japan.
authors: Masayuki
authors: M
authors: Sekiguchi
mesh_terms: D000818:Animals; D066272:Basolateral Nuclear Complex / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry; D003213:Conditioning, Psychological / Q000187:drug effects; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology*; D015525:Fatty Acids, Omega-3 / Q000378:metabolism / Q000494:pharmacology*; D043371:Fatty Acids, Omega-6 / Q000378:metabolism / Q000494:pharmacology*; D005239:Fear / Q000187:drug effects*; D008297:Male; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D017966:Pyramidal Cells / Q000187:drug effects; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*
chemical_list: D004042:Dietary Fats, Unsaturated; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D043884:Receptor, Cannabinoid, CB1