論文

査読有り
2018年

Chronopharmacological Analysis of Antidepressant Activity of a Dual-Action Serotonin Noradrenaline Reuptake Inhibitor (SNRI), Milnacipran, in Rats.

Biological & pharmaceutical bulletin
  • Hiroshi Kawai
  • ,
  • Megumi Machida
  • ,
  • Takuya Ishibashi
  • ,
  • Naomi Kudo
  • ,
  • Yoichi Kawashima
  • ,
  • Atsushi Mitsumoto

41
2
開始ページ
213
終了ページ
219
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1248/bpb.b17-00733

Biological rhythms are thought to be related to the pathogenesis and therapy of various diseases including depression. Here we investigated the influence of circadian rhythms on the antidepressant activity of the dual-action serotonin-noradrenaline reuptake inhibitor (SNRI) milnacipran. Rats administered milnacipran in the morning (8:00 a.m.; zeitgeber time [ZT]1) or in the evening (8:00 p.m.; ZT13) were analyzed in a forced swim test (FST). At ZT1, the rats' immobility was reduced and the swimming was increased, whereas at ZT13, their climbing was increased. These results suggest that the serotonergic and noradrenergic systems are preferentially affected at ZT1 and ZT13, respectively by milnacipran. We analyzed the plasma and brain levels of milnacipran after administration, and there were no differences between ZT1 and ZT13. The circadian rhythm of monoamine neurotransmitters was analyzed in several brain regions. The serotonin turnover showed rhythms with a peak during ZT18-ZT22 in hippocampus. The noradrenaline turnover showed rhythms with a peak during ZT22-ZT2. There was a difference of approx. 4 h between the serotonergic and noradrenergic systems. This time difference might be one of the factors that affect the action of milnacipran and contribute to the dosing time-dependent behavioral pattern in the FST.

リンク情報
DOI
https://doi.org/10.1248/bpb.b17-00733
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29386481

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