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Ingestive Behavior and Neurosciences

Long-Chain Polyunsaturated Fatty Acids Modulate Interleukin-1β–Induced Changes in Behavior, Monoaminergic Neurotransmitters, and Brain Inflammation in Rats^1,2

³ Department of Biomedical Sciences, University of Prince Edward Island, Charlottetown, Canada C1A 4P3; and ⁴ Amarin Neuroscience/Laxdale Ltd, Oxford, UK OX4 4GA

^* To whom correspondence should be addressed. E-mail: cai.song{at}nrc.gc.ca.

Recent evidence has suggested that an imbalance between membrane (n-3) and (n-6) fatty acids may contribute to the etiology of autoimmune and neurodegenerative diseases. In this study, the mechanisms by which eicosapentaenoic acid (EPA), -linolenic acid (GLA), and arachidonic acid (AA) modulate neurotransmitters, behavior, and brain inflammation were evaluated in rats that received central saline or interleukin-1β (IL-1) administrations. In rats treated with saline, only the AA-enriched diet significantly increased anxiety-like behavior in the elevated plus maze, which was associated with increased corticosterone secretion. AA also increased the turnover of dopamine (DA), noradrenaline (NA), and serotonin (5-HT) in the amygdala and increased the prostaglandin (PG)E₂ level in the hippocampus. IL-1 administration slowed rat learning in the water maze and increased anxiety-like behavior, changes which were associated with increased homovanillic acid and 5-HT turnover, decreased NA in the hippocampus and amygdala, decreased DA in the frontal cortex, and decreased IL-10 in limbic brain regions. Increased corticosterone secretion following IL-1 administration was accompanied by increased NA turnover in the hippocampus (P < 0.05) and increased PGE₂ concentration (P < 0.01) in the limbic brain regions. Of the 3 diets tested, only EPA attenuated IL-1–induced behavioral changes (P < 0.05 or 0.01), which was associated with the modulation of EPA on the neuroendocrine and immune changes induced by IL-1. GLA reduced hippocampal PGE₂ concentration in rats given IL-1 (P < 0.01). AA did not counteract any of the changes induced by IL-1. These results suggest that EPA, GLA, and AA play different roles in the neuroendocrine-immune network.