Participation of the nucleus accumbens dopaminergic system in the antidepressant-like actions of a diet rich in omega-3 polyunsaturated fatty acids
Participation of the nucleus accumbens dopaminergic system in the antidepressant-like actions of a diet rich in omega-3 polyunsaturated fatty acids
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DOI：
10.1371/journal.pone.0230647
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发表时间：
2020-03
期刊：
影响因子：
3.7
通讯作者：
E. Takeuchi;Daisuke Yamada;Satoshi Suzuki;A. Saitoh;M. Itoh;Takashi Hayashi;M. Yamada;K. Wada;M. Sekiguchi
中科院分区：
文献类型：
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作者：
E. Takeuchi;Daisuke Yamada;Satoshi Suzuki;A. Saitoh;M. Itoh;Takashi Hayashi;M. Yamada;K. Wada;M. Sekiguchi
补充omega（ω）-3多不饱和脂肪酸（PUFA）对重度抑郁症的有益作用已被积极研究，但其潜在机制仍不清楚。本研究探讨了高ω-3多不饱和脂肪酸饮食小鼠行为变化中多巴胺能神经系统的参与。在强迫游泳试验（FST）中，喂食含有约两倍量ω-3 PUFA的饲料（磷虾油（KO）饲料）的小鼠比喂食仅含α-亚麻酸（ALA）作为ω-3 PUFA的对照饲料的小鼠表现出更短的不动时间。在雄性和雌性小鼠中均观察到不动时间较短。多巴胺代谢产物，3，4-二羟基苯乙酸，增加了NAc在雄性小鼠喂食KO饮食时，与那些喂食对照饮食。此外，多巴胺，3-甲氧基酪胺，高香草酸增加，在NAc的雌性小鼠喂KO饮食。值得注意的是，KO饮食对FST中不动时间的影响通过向NAc中微量注射舒必利（一种D2样受体拮抗剂）而消除。类似的D1样受体，SKF83566的选择性拮抗剂的微量注射，也取消了减少不动性的FST。此外，我们发现，酪氨酸羟化酶阳性细胞增加，在腹侧被盖区（VTA）的小鼠喂KO饮食。这些结果表明，VTA-NAc多巴胺能通路的调节是富含ω-3 PUFA的KO饮食减少小鼠FST中不动行为的机制之一。
The beneficial effects of omega (ω)-3 polyunsaturated fatty acid (PUFA) supplementation on major depressive disorder have been actively studied, but the underlying mechanism remains unknown. The present study examined the involvement of the nucleus accumbens (NAc) dopaminergic systems in behavioral changes in mice fed a diet high in ω-3 PUFAs. Mice fed a diet containing about double the amount of ω-3 PUFAs (krill oil (KO) diet) exerted shorter immobility times in the forced swim test (FST) than mice fed a control diet, containing only α-linolenic acid (ALA) as ω-3 PUFAs. The shorter immobility times were observed in both male and female mice. A dopamine metabolite, 3,4-dihydroxyphenylacetic acid, increased in the NAc in male mice fed the KO diet when compared with those fed the control diet. In addition, dopamine, 3-methoxytyramine, and homovanillic acid increased in the NAc in female mice fed the KO diet. Notably, the effects of the KO diet on the immobility time in the FST were abolished by microinjection of sulpiride, an antagonist of D2-like receptors, into the NAc. A similar microinjection of an antagonist selective for D1-like receptors, SKF83566, also abolished the reduction in immobility in the FST. Moreover, we found that tyrosine hydroxylase-positive cells increased in the ventral tegmental area (VTA) in mice fed the KO diet. These results suggest that modulation of the VTA-NAc dopaminergic pathway is one of the mechanisms by which a KO diet rich in ω-3 PUFAs reduces the immobility behavior in the mouse FST.