Dietary intervention with omega-3 polyunsaturated fatty acids restores decreased dopaminergic activity in the prefrontal cortex of cow's milk allergic mice

Objective: The dopaminergic system in the prefrontal cortex (PFC) is known to modulate attentional skills, organization of thought and perception and social behavior. Supporting these findings, decreased levels of dopamine in the PFC are implicated to be involved in schizophrenia, ADHD and autism. Besides an altered dopaminergic system, disturbed levels of polyunsaturated fatty acid (PUFA) in blood have also been observed in these psychiatric disorders. Beneficial effects of PUFA on behavior of schizophrenia, ADHD and autism have been described, in both human and animal studies. However, larger studies are required to confirm these effects and little is known about the pathway in which PUFA can modulate behavior. We set up a mouse model for cow's milk allergy (CMA) that exerts aberrant social behavior and altered dopaminergic activation in the PFC. The aim of this study was to investigate whether dietary intervention with PUFA can modulate altered dopamine levels in the PFC, which are associated with behavior in these allergic mice. Methods: Male C3H/HeOuJ mice were orally sensitized with whey protein and cholera toxin (CT) or CT alone, once a week for 5 weeks and subsequently orally challenged with whey protein once. Starting two weeks before first sensitization, mice were kept on an omega-3 PUFA diet or control diet. The morning after challenge, mice were sacrificed and brains were collected. Prefrontal cortex (PFC) was isolated and dopamine levels were determined by using HPLC. Results: Dopamine levels were significantly decreased in PFC of CMA mice compared to controls. A dietary intervention with omega-3 PUFA completely restored the levels to those found in control (non-allergic) mice. Levels of three metabolites of dopamine (HVA, 3-MT and DOPAC) were also significantly decreased in the PFC of CMA mice. The omega-3 PUFA diet also restored these metabolites to control levels. Conclusions: Cow's milk allergy in mice caused a significant decrease in dopamine and its metabolite levels in the PFC and a dietary intervention with omega-3 PUFA restored the levels to those found in control mice. Therefore, PUFA possibly exerts its beneficial effect on normalizing behavior via modulation of the dopaminergic system in the PFC and might offer a dietary intervention in some psychiatric disorders.