Lifelong imbalanced linoleic/alpha-linolenic acid intake impairs emotional and cognitive behavior in adult rats via changes in brain endocannabinoid system.

Imbalanced dietary n-3 and n-6 PUFA content has been associated with a number of neurological conditions. Endocannabinoids are n-6 PUFA derivatives, whose brain concentrations are sensitive to modifications of fatty acid composition of the diet, and play a central role in the regulation of mood and cognition. As such, the endocannabinoid system appears to be an ideal candidate for mediating the effects of dietary fatty acids on mood and cognition. Lifelong administration of isocaloric alpha linolenic acid (ALA) deficient and enriched diets induced short-term memory deficits, whereas only dietary ALA enrichment altered emotional reactivity in adult male rats compared to animals fed a standard diet, balanced in ALA/linoleic (LA) ratio. In the prefrontal cortex, both diets reduced 2-AG levels and increased MAG lipase expression, whereas only the enriched diet reduced AEA levels, simultaneously increasing FAAH expression. In the hippocampus, ALA enriched diet decreased AEA content and NAPE-PLD expression, and reduced 2-AG content while increasing MAG lipase expression. These findings highlight the importance of a diet balanced in fatty acid contents for normal brain functions and support a link between dietary ALA, brain endocannabinoid system and behavior, indicating that dietary ALA intake is a sufficient condition for altering the endocannabinoid system in brain regions modulating mood and cognition.