Abstract
BackgroundPrevious reports suggest that omega-3 (n-3) polyunsaturated fatty acids (PUFA) supplements may reduce ADHD-like behaviour. Our aim was to investigate potential effects of n-3 PUFA supplementation in an animal model of ADHD.MethodsWe used spontaneously hypertensive rats (SHR). SHR dams were given n-3 PUFA (EPA and DHA)-enriched feed (n-6/n-3 of 1:2.7) during pregnancy, with their offspring continuing on this diet until sacrificed. The SHR controls and Wistar Kyoto (WKY) control rats were given control-feed (n-6/n-3 of 7:1). During postnatal days (PND) 25–50, offspring were tested for reinforcement-dependent attention, impulsivity and hyperactivity as well as spontaneous locomotion. The animals were then sacrificed at PND 55–60 and their neostriata were analysed for monoamine and amino acid neurotransmitters with high performance liquid chromatography.Resultsn-3 PUFA supplementation significantly enhanced reinforcement-controlled attention and reduced lever-directed hyperactivity and impulsiveness in SHR males whereas the opposite or no effects were observed in females. Analysis of neostriata from the same animals showed significantly enhanced dopamine and serotonin turnover ratios in the male SHRs, whereas female SHRs showed no change, except for an intermediate increase in serotonin catabolism. In contrast, both male and female SHRs showed n-3 PUFA-induced reduction in non-reinforced spontaneous locomotion, and sex-independent changes in glycine levels and glutamate turnover.ConclusionsFeeding n-3 PUFAs to the ADHD model rats induced sex-specific changes in reinforcement-motivated behaviour and a sex-independent change in non-reinforcement-associated behaviour, which correlated with changes in presynaptic striatal monoamine and amino acid signalling, respectively. Thus, dietary n-3 PUFAs may partly ameliorate ADHD-like behaviour by reinforcement-induced mechanisms in males and partly via reinforcement-insensitive mechanisms in both sexes.
Highlights
Attention deficit hyperactivity disorder (ADHD) which affects ~5% of children [1] is characterized by attention deficit, hyperactivity and impulsiveness [2], with three times higher prevalence among boys than girls [3]
Humans are able to synthesize the omega-6 (n-6) fatty acid (FA) arachidonic acid (AA) from linoleic acid (LA), and the n-3 FAs like eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from alpha-linolenic acid (ALA), these processes are slow and ineffective in most mammals [10], and they are influenced by different factors like sex hormones, n-6/n-3 intake ratio and saturated fatty acid intake
Our results indicate that n-3 polyunsaturated fatty acids (PUFA) feeding may ameliorate reinforcement- and monoaminedependent ADHD symptoms in a sex-specific manner, whereas other symptoms, independent of reinforcement and possibly correlated to changes in amino acid transmitters, were ameliorated to the same extent in both sexes
Summary
Attention deficit hyperactivity disorder (ADHD) which affects ~5% of children [1] is characterized by attention deficit, hyperactivity and impulsiveness [2], with three times higher prevalence among boys than girls [3]. The concordance of monozygotic twins is not perfect, suggesting that environmental factors may act in additive or interactive ways with the genetic influence [5,6]. The cognitive dysfunction in ADHD may be affected by a lack of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) during embryonic development and early life [7,8,9]. Humans are able to synthesize the omega-6 (n-6) fatty acid (FA) arachidonic acid (AA) from linoleic acid (LA), and the n-3 FAs like eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from alpha-linolenic acid (ALA), these processes are slow and ineffective in most mammals [10], and they are influenced by different factors like sex hormones, n-6/n-3 intake ratio and saturated fatty acid intake. Previous reports suggest that omega-3 (n-3) polyunsaturated fatty acids (PUFA) supplements may reduce ADHD-like behaviour. Our aim was to investigate potential effects of n-3 PUFA supplementation in an animal model of ADHD
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