Gender-dependent and genotype-sensitive monoaminergic changes induced by polychlorinated biphenyl 153 in the rat brain

Polychlorinated biphenyls (PCBs) are present as ortho- and non-ortho-substituted PCBs, with most of the ortho-substituted congeners being neurotoxic. The present study examined effects of the ortho-substituted PCB 153 on dopamine, serotonin and amino acid neurotransmitters in the neostriatum of both male and female Wistar Kyoto (WKY) and spontaneously hypertensive rat (SHR) genotypes. PCB 153 exposure at p8, p14 and p20 had no effects on levels of these transmitters when examined at p55, but led to increased levels of both homovanillic acid and 5-hydroxyindoleacetic acid, the degradation products of dopamine and serotonin, respectively, in all groups except the female SHR. Immunoblotting showed that PCB exposure induced gender-specific decreases in dopaminergic synaptic proteins. These included a novel finding of decreased levels of the dopamine D5 receptor in both genders and genotypes, whereas male-specific changes included decreases in the postsynaptic density (PSD)-95 protein in the WKY and SHRs and a decrease in the presynaptic dopamine transporter in both the WKY and, less clearly in the male SHR. A female-specific tendency of increased vesicular monoamine transporter-2 was observed in the SHRs after PCB exposure. No changes were seen in tyrosine hydroxylase, the cytoskeletal neurotubulin or the plasma membrane marker Na+/K+-ATPase in any strain. Hence, PCB-exposure led to increases in monoamine transmitter turnover in both male and female animals, whereas decreases in both pre- and postsynaptic dopaminergic proteins were predominantly seen in male animals. PCB 153 may therefore induce neostriatal toxicity through both presynaptic and postsynaptic mechanisms in both genotypes and genders, including effects on the aspiny interneurons, which employ the D5 receptor to mediate dopamine effects on interneurons in the basal ganglia

Marine omega-3 polyunsaturated fatty acids induce sex-specific changes in reinforcer-controlled behaviour and neurotransmitter metabolism in a spontaneously hypertensive rat model of ADHD

Background 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. Methods We 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. Results n-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. Conclusions Feeding 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

Marine omega-3 polyunsaturated fatty acids induce sex-specific changes in reinforcer-controlled behaviour and neurotransmitter metabolism in a spontaneously hypertensive rat model of ADHD

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. Methods We 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. Results n-3 PUFA-feeding improved reinforcement-induced attention in males but not in female SHRs. 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. Conclusions Feeding n-3 PUFAs to the ADHD model rats induced sex-specific changes in reinforcementmotivated 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 reinforcementinsensitive mechanisms in both sexe