Insufficient availability of n-3 polyunsaturated fatty acids (PUFA) during pre- and neonatal development decreases accretion of docosahexaenoic acid (DHA, 22:6n-3) in the developing brain. Low tissue levels of DHA are associated with neurodevelopmental disorders including attention deficit hyperactivity disorder (ADHD). In this study, 1st- and 2nd-litter male Long-Evans rats were raised from conception on a Control diet containing alpha-linolenic acid (4.20 g/kg diet), the dietarily essential fatty acid precursor of DHA, or a diet Deficient in alpha-linolenic acid (0.38 g/kg diet). The Deficient diet resulted in a decrease in brain phospholipid DHA of 48% in 1st-litter pups and 65% in 2nd-litter pups. Activity, habituation, and response to spatial change in a familiar environment were assessed in a single-session behavioral paradigm at postnatal days 28 and 70, inclusive. Activity and habituation varied by age with younger rats exhibiting higher activity, less habituation, and less stimulation of activity induced by spatial novelty. During the first and second exposures to the test chamber, 2nd-litter Deficient pups exhibited higher levels of activity than Control rats or 1st-litter Deficient pups, and less habituation during the first exposure, but were not more active after introduction of a novel spatial stimulus. The higher level of activity in a familiar environment, but not after introduction of a novel stimulus is consistent with clinical observations in ADHD. The observation of this effect only in 2nd-litter rats fed the Deficient diet suggests that brain DHA content, rather than dietary n-3 PUFA content, likely underlies these effects.
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