The postnatal 5-HT1A receptor regulates adult anxiety and depression differently via multiple molecules

作者：Ishikawa Chihiro; Shiga Takashi^*

来源：Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2017, 78: 66-74.

DOI：10.1016/j.pnpbp.2017.04.014

• 5-HT1A receptor
• GABAA receptor
• BDNF
• Anxiety
• Depression

Serotonin (5-HT) and the 5-HT1A 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-HT1A 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-HT1A receptor, brain-derived neurotrophic factor (BDNF), GABA(A) 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-HT1A 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(A) receptor alpha 3 subunit in the mPFC and ventral hippocampus in adulthood, while 8-OH-DPAT, but not fluoxetine, decreased the mRNA expression of the 5-HT1A receptor and BDNF in the mPFC and the GABA(A) receptor alpha 2 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(A) receptor alpha 3 subunit in the mPFC and ventral hippocampus may regulate anxiety-like behavior. In contrast, depression-like behavior may be regulated by the 5-HT1A receptor and BDNF in the mPFC and by the GABA(A) receptor alpha 2 subunit in the mPFC and ventral hippocampus. In summary, activation of the 5-HT1A 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.

• 出版日期2017-8-1