We studied the effects of a fish oil enriched diet on fatty acid composition of cerebral membranes and on several neurochemical and behavioral variables of monoaminergic function in rats. The frontal cortex, striatum, hippocampus and cerebellum were studied in rats fed fish oil (FPO, 50% salmon oil + 50% palm oil), which provided an (n-6)/(n-3) polyunsaturated fatty acid (PUFA) ratio of 0.14 versus 6. 19 in controls fed a diet containing a mixture of African peanut oil and rapeseed oil. In the FPO group compared to the control group, the major modifications in fatty acid composition of cerebral membranes included the following: higher levels in 22:6(n-3), lower levels in 20:4(n-6) and a significantly greater proportion of phosphatidylserine. Dopamine levels were 40% greater in the frontal cortex of rats fed FPO than from those fed the control diet. In this cerebral region there was also a reduction in monoamine oxidase B (MAO-B) activity and greater binding to dopamine D2 receptors. By contrast, a lower binding to dopamine D2 receptors (-7%) was observed in the striatum. Ambulatory activity was also reduced in FPO-fed rats, possibly related to observed changes in striatal dopaminergic receptors. This suggested that the level of (n-6) PUFA, which was considerably lower in the FPO diet than in the control diet, could act on locomotion through an effect on striatal dopaminergic function, whereas the high level of (n-3) PUFA could act on cortical dopaminergic function.

We studied the effects of a diet chronically deficient in ␣ -linolenic acid, the precursor of long-chain n-3 polyunsaturated fatty acids, on dopaminergic neurotransmission in the shell region of the nucleus accumbens of rats. In vivo microdialysis experiments showed increased basal levels of dopamine and decreased basal levels of metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in awake rats from the deficient group compared to controls. The release of dopamine under KCl stimulation was similar in both dietary groups. By contrast, the release of dopamine from the vesicular storage pool under tyramine stimulation was 90% lower in the deficient than in the control rats. Autoradiographic studies in the same cerebral region revealed a 60% reduction in the vesicular monoamine transporter sites in the deficient group. Dopamine D 2 receptors were 35% increased in these rats compared to controls, whereas no change occurred for D 1 receptors and membrane dopamine transporters. These results demonstrated that chronic n-3 polyunsaturated fatty acid deficiency modifies several factors of dopaminergic neurotransmission in the nucleus accumbens. These findings are in agreement with the changes in dopaminergic neurotransmission already observed in the frontal cortex, and with the behavioral disturbances described in these deficient rats.

In rodents, chronic dietary alpha-linolenic acid deficiency decreases learning and memory and alters dopaminergic and serotoninergic neurotransmission. However, these two neurotransmitter systems are related mainly to attention, emotion and locomotion. Therefore, we decided to investigate the effects of dietary alpha-linolenic acid deficiency in rats tested with animal models of distractibility (the distractometer procedure), anxiety (the elevated plus maze) and ambulatory activity (a circular corridor). Moreover, because these neurochemical modifications persist during aging, we decided to study the effects of aging on these behaviors by using rats aged 2, 6, 12 and 24 mo. An age-related decline in distractibility was observed that was accelerated by linolenic acid deficiency. Indeed, an age-related reduction in distractibility was found in so far as distraction time was reduced at the age of 12 mo in controls and at the age of 24 mo in deficient groups compared with 2-mo-old rats. Moreover, distraction time was significantly lower in 6- and 24-mo-old rats fed a deficient diet compared with age-matched controls. Anxiety was not modified by diet or age. Finally, a parallel decrease in locomotion was exhibited by rats fed both diets between 6 and 12 mo of age. Locomotion was not modified by diet. These results show that dietary alpha-linolenic deficiency alters behavior in a very specific way; distractibility is modified by diet, whereas anxiety and locomotion are not, suggesting that particular brain areas may be altered.

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