Nutritional n-3 polyunsaturated fatty acids deficiency alters cannabinoid receptor signaling pathway in the brain and associated anxiety-like behavior in mice

Thomas Larrieu; Charlotte Madore; Corinne Joffre; Sophie Layé

doi:10.1007/s13105-012-0179-6

Nutritional n-3 polyunsaturated fatty acids deficiency alters cannabinoid receptor signaling pathway in the brain and associated anxiety-like behavior in mice

J Physiol Biochem. 2012 Dec;68(4):671-81. doi: 10.1007/s13105-012-0179-6. Epub 2012 Jun 16.

Authors

Thomas Larrieu¹, Charlotte Madore, Corinne Joffre, Sophie Layé

Affiliation

¹ Nutrition et Neurobiologie Intégrée, INRA UMR 1286, Bâtiment UFR Pharmacie 2° tranche, 2° étage, Case courrier 34, Université Victor Ségalen, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France.

PMID: 22707188
DOI: 10.1007/s13105-012-0179-6

Abstract

N-3 polyunsaturated fatty acids (PUFAs) cannot be synthesized de novo in mammals and need to be provided by dietary means. In the brain, the main n-3 PUFA is docosahexaenoic acid (DHA), which is a key component of neuronal membranes. A low dietary level of DHA has been associated with increased risk of developing neuropsychiatric diseases; however, the mechanisms involved remain to be determined. In this study, we found that long-term exposure to an n-3 deficient diet decreases the level of DHA in the brain and impairs the cannabinoid receptor signaling pathway in mood-controlling structures. In n-3 deficient mice, the effect of the cannabinoid agonist WIN55,212-2 in an anxiety-like behavior test was abolished. In addition, the cannabinoid receptor signaling pathways were altered in the prefrontal cortex and the hypothalamus. Consequently, our data suggest that behavioral changes linked to an n-3 dietary deficiency are due to an alteration in the endocannabinoid system in specific brain areas.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anxiety / metabolism*
Benzoxazines / pharmacology
Brain / metabolism*
Cannabinoid Receptor Agonists / pharmacology
Early Growth Response Protein 1 / genetics
Early Growth Response Protein 1 / metabolism
Endocannabinoids / physiology
Fatty Acids, Omega-3 / metabolism*
Female
MAP Kinase Signaling System*
Malnutrition / metabolism*
Malnutrition / psychology
Mice
Mice, Inbred C57BL
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism
Morpholines / pharmacology
Motor Activity
Naphthalenes / pharmacology
Receptors, Cannabinoid / metabolism*
Social Behavior

Substances

Benzoxazines
Cannabinoid Receptor Agonists
Early Growth Response Protein 1
Egr1 protein, mouse
Endocannabinoids
Fatty Acids, Omega-3
Morpholines
Naphthalenes
Receptors, Cannabinoid
(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3