Ishikawa Chihiro, Shiga Takashi
Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan.
Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan; Department of Neurobiology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan.
Prog Neuropsychopharmacol Biol Psychiatry. 2017 Aug 1;78:66-74. doi: 10.1016/j.pnpbp.2017.04.014. Epub 2017 May 5.
Serotonin (5-HT) and the 5-HT receptor during development are known to modulate anxiety and depression in later life. However, the brain mechanisms linking the postnatal 5-HT system and adult behavior remain unknown. Here, we examined the effects of pharmacological 5-HT receptor activation during the postnatal period on anxiety and depression-like behavior in adult BALB/c male mice. To elucidate the underlying mechanisms, we measured mRNA expression of the 5-HT receptor, brain-derived neurotrophic factor (BDNF), GABA receptor subunits, and AMPA receptor subunits in the medial prefrontal cortex (mPFC), amygdala, and hippocampus. Treatment with the selective 5-HT reuptake inhibitor (fluoxetine) and 5-HT receptor agonist (8-OH-DPAT) during the postnatal period decreased anxiety-like behavior in adulthood, whereas only 8-OH-DPAT treatment increased depression-like behavior. Concomitantly with the behavioral effects, postnatal treatment with fluoxetine and 8-OH-DPAT decreased the mRNA expression of the GABA receptor α3 subunit in the mPFC and ventral hippocampus in adulthood, while 8-OH-DPAT, but not fluoxetine, decreased the mRNA expression of the 5-HT receptor and BDNF in the mPFC and the GABA receptor α2 subunit in the mPFC and ventral hippocampus. On the basis of the correlative changes between behavior and mRNA expression, these results suggest that the GABA receptor α3 subunit in the mPFC and ventral hippocampus may regulate anxiety-like behavior. In contrast, depression-like behavior may be regulated by the 5-HT receptor and BDNF in the mPFC and by the GABA receptor α2 subunit in the mPFC and ventral hippocampus. In summary, activation of the 5-HT receptor during the postnatal period may reduce anxiety levels, but increase depression levels during adulthood via different multiple molecules in the mPFC and ventral hippocampus.
已知血清素（5-羟色胺，5-HT）及其受体在发育过程中会调节成年后的焦虑和抑郁。然而，产后5-HT系统与成年行为之间的大脑机制仍不清楚。在此，我们研究了产后期间药理学上激活5-HT受体对成年BALB/c雄性小鼠焦虑和抑郁样行为的影响。为了阐明潜在机制，我们测量了内侧前额叶皮质（mPFC）、杏仁核和海马体中5-HT受体、脑源性神经营养因子（BDNF）、GABA受体亚基和AMPA受体亚基的mRNA表达。产后期间用选择性5-HT再摄取抑制剂（氟西汀）和5-HT受体激动剂（8-OH-DPAT）治疗可降低成年后的焦虑样行为，而只有8-OH-DPAT治疗会增加抑郁样行为。与行为效应相伴的是，产后用氟西汀和8-OH-DPAT治疗会降低成年后mPFC和腹侧海马体中GABA受体α3亚基的mRNA表达，而8-OH-DPAT（而非氟西汀）会降低mPFC中5-HT受体和BDNF以及mPFC和腹侧海马体中GABA受体α2亚基的mRNA表达。基于行为与mRNA表达之间的相关变化，这些结果表明mPFC和腹侧海马体中的GABA受体α3亚基可能调节焦虑样行为。相比之下，抑郁样行为可能由mPFC中的5-HT受体和BDNF以及mPFC和腹侧海马体中的GABA受体α2亚基调节。总之，产后期间激活5-HT受体可能会降低焦虑水平，但会通过mPFC和腹侧海马体中的不同多种分子在成年期增加抑郁水平。
