TY - JOUR
T1 - Lithium counteracts depressive behavior and augments the treatment effect of selective serotonin reuptake inhibitor in treatment-resistant depressed rats
AU - Kin, Kyohei
AU - Yasuhara, Takao
AU - Kawauchi, Satoshi
AU - Kameda, Masahiro
AU - Hosomoto, Kakeru
AU - Tomita, Yousuke
AU - Umakoshi, Michiari
AU - Kuwahara, Ken
AU - Kin, Ittetsu
AU - Kidani, Naoya
AU - Morimoto, Jun
AU - Sasaki, Tatsuya
AU - Date, Isao
N1 - Funding Information:
This research was supported by grants for Scientific Research from the Ministry of Health, Labor and Welfare of Japan ( 09156274 and 24592129 ). We thank Masako Arao and Yoshie Ukai for their technical assistance.
Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2019/8/15
Y1 - 2019/8/15
N2 - 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.
AB - 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.
KW - Depression
KW - Fluoxetine
KW - Hippocampus
KW - Lithium
KW - Neurogenesis
KW - Wistar Kyoto rat
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U2 - 10.1016/j.brainres.2019.04.001
DO - 10.1016/j.brainres.2019.04.001
M3 - Article
C2 - 30953607
AN - SCOPUS:85064199567
SN - 0006-8993
VL - 1717
SP - 52
EP - 59
JO - Molecular Brain Research
JF - Molecular Brain Research
ER -