Sex-specific effects of brain LC-PUFA composition on locomotor activity in rats

Abstract

Insufficient availability of n − 3 polyunsaturated fatty acids (PUFAs) during pre- and neonatal development decreases accretion of docosahexaenoic acid (DHA, 22:6 n − 3) in the developing brain and is associated with sub-optimal sensory and cognitive function in humans, altered behavior in animals, and may contribute to neurodevelopmental disorders such as attention deficit hyperactivity disorder and schizophrenia. This study examined the effects of variation in dietary availability of n − 3 PUFAs on brain fatty acid composition and the consequent effects on locomotor activity in male and female Long–Evans rats. Rats were raised from conception using purified diets and breeding protocols designed to produce four groups with distinct brain phospholipid compositions varying in DHA content and/or the proportion of n − 3 and n − 6 PUFAs. Locomotor behavior was measured for a 2-h period on postnatal days 28, 42, 56, and 70. In males, decreased brain DHA produced alterations in activity that were most pronounced post-adolescence and with the greatest decrease in DHA. However, the behavioral effects in males were not linearly related to brain DHA level. In contrast, no significant effects of variation in brain fatty acid composition were observed in females. This suggests that variation in brain DHA content produces sex-specific alterations in locomotor activity and that the neurochemical alterations underlying the observed behavioral changes vary depending on the degree of DHA depletion.