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Repeated ketamine administration redeems the time lag for citalopram's antidepressant-like effects

Published online by Cambridge University Press:  15 April 2020

G.-F. Zhang ,
W.-X. Liu ,
L.-L. Qiu ,
J. Guo ,
X.-M. Wang ,
H.-L. Sun ,
J.-J. Yang  and
Z.-Q. Zhou
G.-F. Zhang
Affiliation:
Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing210002, China
W.-X. Liu
Affiliation:
Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing210002, China
L.-L. Qiu
Affiliation:
Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing210002, China
J. Guo
Affiliation:
Department of Anesthesiology, Affiliated Hospital of Nanjing, University of Traditional Chinese Medicine, Nanjing, China
X.-M. Wang
Affiliation:
Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing210002, China
H.-L. Sun
Affiliation:
Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing210002, China
J.-J. Yang*
Affiliation:
Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing210002, China Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, China Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou, China
Z.-Q. Zhou*
Affiliation:
Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing210002, China
*
⁎⁎Co-corresponding author. Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China. E-mail addresses:yjyangjj@126.com (J.-J. Yang)
*Corresponding author. Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China. Tel.: +86 25 52323834; fax: +86 25 84806839. E-mail addresses:zq-zhou@163.com (Z.-Q. Zhou).
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Abstract

Current available antidepressants exhibit low remission rate with a long response lag time. Growing evidence has demonstrated acute sub-anesthetic dose of ketamine exerts rapid, robust, and lasting antidepressant effects. However, a long term use of ketamine tends to elicit its adverse reactions. The present study aimed to investigate the antidepressant-like effects of intermittent and consecutive administrations of ketamine on chronic unpredictable mild stress (CUMS) rats, and to determine whether ketamine can redeem the time lag for treatment response of classic antidepressants. The behavioral responses were assessed by the sucrose preference test, forced swimming test, and open field test. In the first stage of experiments, all the four treatment regimens of ketamine (10 mg/kg ip, once daily for 3 or 7 consecutive days, or once every 7 or 3 days, in a total 21 days) showed robust antidepressant-like effects, with no significant influence on locomotor activity and stereotype behavior in the CUMS rats. The intermittent administration regimens produced longer antidepressant-like effects than the consecutive administration regimens and the administration every 7 days presented similar antidepressant-like effects with less administration times compared with the administration every 3 days. In the second stage of experiments, the combination of ketamine (10 mg/kg ip, once every 7 days) and citalopram (20 mg/kg po, once daily) for 21 days caused more rapid and sustained antidepressant-like effects than citalopram administered alone. In summary, repeated sub-anesthestic doses of ketamine can redeem the time lag for the antidepressant-like effects of citalopram, suggesting the combination of ketamine and classic antidepressants is a promising regimen for depression with quick onset time and stable and lasting effects.

Keywords

DepressionKetamineCitalopramBehavior
Type
Original article
Information
European Psychiatry , Volume 30 , Issue 4 , June 2015 , pp. 504 - 510
Copyright
Copyright © Elsevier Masson SAS 2015

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Footnotes

1

The two authors contributed equally to this work.

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