This study investigated the effects of varying dietary levels of very long-chain polyunsaturated fatty acids on growth, brain fatty acid composition and behavior in mice. Five groups of pregnant and lactating B6D2F1 mice were fed diets with either a very high (n-6):(n-3) ratio of 49 [(n-3) deficient)], a normal ratio of 4.0 or a low ratio of 0.32. The (n-6) fatty acids (FA) were provided either entirely as linoleic acid (LA) or as LA in combination with arachidonic acid (ARA), and the (n-6):(n-3) ratios were adjusted by partial replacement of the (n-6) FA with docosahexaenoic acid (DHA). Offspring were maintained on these diets after weaning. The diets with the low (n-6): (n-3) ratio had no effect on the birth weights of the pups, but after 15 d resulted in a significant 12% reduction in body weights. This effect persisted to adulthood and was apparent in both brain and body weights unless ARA was substituted partially for LA as the source of (n-6) FA. There were significant effects of diet on brain fatty acid composition. Increasing levels of DHA in the diet increased brain DHA and decreased ARA, and there was also retroconversion of DHA in EPA in the mice fed high levels of DHA. Addition of ARA to the diet increased brain ARA, and, at high levels only, decreased DHA. There were no effects of this wide variation in dietary (n-6):(n-3) ratio on the ability of the mice to learn the place of the hidden platform in the Morris water maze. However, in both the cued and the place learning, the mice fed the low (n-6):(n-3) diet swam more slowly, unless ARA substituted partially for LA as the source of (n-6) FA. There were no effects of diet on activity in the spatial open field. These findings show that the effects of a diet with a low (n-6):(n-3) ratio and (n-3) FA provided as DHA, can be overcome if LA is partially replaced by ARA as the source of (n-6) FA.

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Feeding mice a diet deficient in n-3 fatty acids for three generations resulted in a 53% decrease in docosahexaenoic acid (DHA, 22:6n-3) in the brain. Maternal pup retrieval and social learning of a food preference are both tasks based on olfactory function. All dams made contact more readily with pups of their own dietary group, and animals of both dietary groups demonstrated the ability to learn a food preference through exposure to a conspecific that had previously eaten the food. Both groups showed similar ability to learn the location of the hidden platform in the Morris water maze, while the n-3 deficient animals were marginally faster in locating the platform on the cued trial. They were also more active when tested in the open field. While they did not differ in their duration of immobility in a forced swimming test, the deficient animals did have longer paw-lick latencies on a hot plate. Thus, in this study a significant reduction in brain n-3 fatty acid composition, while associated with some indications of change in emotional reactivity, did not impair olfactory function or learning of either a latent or spatial nature.

This study examines the effects of the ratio of n-3/n-6 fatty acids (FA) on brain development in mice when long-chain n-3 FA are supplied in the diet. From conception until 12 days after birth, B6D2F1 mice were fed liquid diets, each providing 10% of energy from olive oil, and a further 10% from different combinations of free FA concentrates derived from safflower oil (18:2n-6), and fish oil (20:5n-3 and 22:6n-3). The range of dietary n-3/n-6 ratios was 0, 0.25, 0.5, 1.0, 2.0 and 4.0, with an n-6 content of greater than 1.5% of energy in all diets, and similar levels of total polyunsaturated fatty acids (PUFA). In an additional group of ratio 0.5, 18:2n-6 was partially replaced by its delta 6 desaturation product, 18:3n-6. Biochemical analyses were conducted on 12-day-old pup brains, as well as on samples of maternal milk. No obvious effects on overall pup growth and development were observed, apart from a smaller litter size at ratio 1. Co-variance analysis indicated that increasing the n-3/n-6 ratio was associated with slightly smaller brains, relative to body weight. We found that 18:2n-6 and 20:5n-3 were the predominant n-6 and n-3 FA in the milk; in the brain these were 20:4n-6 and 22:6n-3, respectively. Increasing dietary n-3/n-6 ratios generally resulted in an increase in n-3 FA, with a corresponding decrease in n-6 FA.(ABSTRACT TRUNCATED AT 250 WORDS)

Artificial rearing (AR) of infant rats permits precise control over key features of the early environment without maternal influence. The present study examined the behavioral response of AR rats towards natural and drug-mediated rewards, as well as their exploratory and affective behaviors. Adolescent AR rats showed increased preference for sucrose consumption relative to chow and demonstrated greater activity in the open field and in the elevated plus-maze compared to maternally reared (MR) rats. With respect to measures of emotionality, AR rats showed enhanced avoidance of the open arms of the plus-maze, indicating increased anxiety, but they did not differ from MR rats in exploring the center of the open field. Adult AR rats displayed a stronger conditioned response to morphine in a place preference test. These findings support the potential of the AR model to contribute to understanding the role of early experience in the development of behavioral motivation.