Lithium counteracts depressive behavior and augments the treatment effect of selective serotonin reuptake inhibitor in treatment-resistant depressed rats

Kyohei Kin, Takao Yasuhara, Satoshi Kawauchi, Masahiro Kameda, Kakeru Hosomoto, Yousuke Tomita, Michiari Umakoshi, Ken Kuwahara, Ittetsu Kin, Naoya Kidani, Jun Morimoto, Tatsuya Sasaki, Isao Date

Research output: Contribution to journalArticle

Abstract

Wistar Kyoto (WKY) rats are a useful animal model of treatment-resistant depression. Lithium is effective for treating recurrent mood disorders or treatment-resistant depression, and lithium augmentation treatment is also useful for treatment-resistant depression. However, the treatment effect of lithium on the depressive behavior of WKY rats remains poorly understood, and whether lithium augments the treatment effect of antidepressants in WKY rats is also unknown. In this study, we evaluated the treatment effect of lithium in WKY rats. We also sought to determine if lithium treatment augments the treatment effect of fluoxetine. Lithium was administered for 15 consecutive days and fluoxetine was administered 23.5, 5, and 1 h before the forced swim test (FST) day 2, based on previous studies. Lithium treatment counteracted depressive behavior in the FST and increased hippocampal neurogenesis. Additionally, co-administration of lithium and fluoxetine augmented the treatment effect observed in the FST and in hippocampal neurogenesis in WKY rats, although fluoxetine monotherapy showed no treatment effect. Lithium prevented an increase in body weight, similar to its effect in human patients. These results are consistent with those of lithium augmentation treatment for human patients with treatment-resistant depression. They suggest that WKY rats are a promising animal model for treatment-resistant depression. However, lithium treatment has various side effects. A new treatment with the same anti-depressive effect as fluoxetine + lithium treatment and fewer side effects compared with lithium would be desirable for patients with treatment-resistant depression.

Original languageEnglish
Pages (from-to)52-59
Number of pages8
JournalBrain Research
Volume1717
DOIs
Publication statusPublished - Aug 15 2019

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Serotonin Uptake Inhibitors
Lithium
Treatment-Resistant Depressive Disorder
Inbred WKY Rats
Fluoxetine
Therapeutics
Neurogenesis
Animal Models
Mood Disorders
Antidepressive Agents

Keywords

  • Depression
  • Fluoxetine
  • Hippocampus
  • Lithium
  • Neurogenesis
  • Wistar Kyoto rat

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this

Lithium counteracts depressive behavior and augments the treatment effect of selective serotonin reuptake inhibitor in treatment-resistant depressed rats. / Kin, Kyohei; Yasuhara, Takao; Kawauchi, Satoshi; Kameda, Masahiro; Hosomoto, Kakeru; Tomita, Yousuke; Umakoshi, Michiari; Kuwahara, Ken; Kin, Ittetsu; Kidani, Naoya; Morimoto, Jun; Sasaki, Tatsuya; Date, Isao.

In: Brain Research, Vol. 1717, 15.08.2019, p. 52-59.

Research output: Contribution to journalArticle

Kin, Kyohei ; Yasuhara, Takao ; Kawauchi, Satoshi ; Kameda, Masahiro ; Hosomoto, Kakeru ; Tomita, Yousuke ; Umakoshi, Michiari ; Kuwahara, Ken ; Kin, Ittetsu ; Kidani, Naoya ; Morimoto, Jun ; Sasaki, Tatsuya ; Date, Isao. / Lithium counteracts depressive behavior and augments the treatment effect of selective serotonin reuptake inhibitor in treatment-resistant depressed rats. In: Brain Research. 2019 ; Vol. 1717. pp. 52-59.
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