Chronopharmacological study of antidepressants in forced swimming test of mice

Kentarou Ushijima, Hiromi Sakaguchi, Yuki Sato, Hideto To, Koyanagi Satoru, Shun Higuchi, Shigehiro Ohdo

Research output: Contribution to journalArticle

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Abstract

The influence of dosing time on the anti-immobility effect of antidepressants and mechanisms underlying this phenomenon were investigated in mice. In the forced swimming test (FST), the immobility time of mice treated with amitriptyline (15 mg/kg) and fluvoxamine (30 mg/kg) showed a significant 24-h rhythm. The anti-immobility effect of fluvoxamine in FST was potent at the early part of the dark phase without increasing locomotor activity. Concerning pharmacokinetics, although Ke of fluvoxamine was approximately 1.3-fold higher in mice injected with fluvoxamine at 9:00 PM than at 9:00 AM, no dosing time dependence was demonstrated for either plasma or brain fluvoxamine concentration at 0.5 h after the drug injection. On the other hand, serotonin transporter (SERT) mRNA expression and 5-hydroxytryptamine (5-HT) uptake activity in the mouse midbrain showed significant time-dependent changes with higher levels during the dark phase and lower levels during the light phase. These results suggest that the reuptake of 5-HT might be more increased during the dark phase. Since the reuptake of 5-HT is inhibited almost completely by injection with 30 mg/kg fluvoxamine at any time, the extracellular 5-HT level may be more increased by the injection of fluvoxamine at the early part of the dark phase. The present results suggest that the antiimmobility effect of fluvoxamine in FST increases depending on dosing time. Furthermore, the time-dependent change of SERT mRNA expression and uptake activity in the midbrain is suggested to be the mechanism underlying the 24-h rhythm of anti-immobility effect of fluvoxamine.

Original languageEnglish
Pages (from-to)764-770
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume315
Issue number2
DOIs
Publication statusPublished - Nov 1 2005

Fingerprint

Fluvoxamine
Antidepressive Agents
Serotonin
Serotonin Plasma Membrane Transport Proteins
Mesencephalon
Injections
Messenger RNA
Amitriptyline
Locomotion
Pharmacokinetics
Light

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

Chronopharmacological study of antidepressants in forced swimming test of mice. / Ushijima, Kentarou; Sakaguchi, Hiromi; Sato, Yuki; To, Hideto; Satoru, Koyanagi; Higuchi, Shun; Ohdo, Shigehiro.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 315, No. 2, 01.11.2005, p. 764-770.

Research output: Contribution to journalArticle

Ushijima, Kentarou ; Sakaguchi, Hiromi ; Sato, Yuki ; To, Hideto ; Satoru, Koyanagi ; Higuchi, Shun ; Ohdo, Shigehiro. / Chronopharmacological study of antidepressants in forced swimming test of mice. In: Journal of Pharmacology and Experimental Therapeutics. 2005 ; Vol. 315, No. 2. pp. 764-770.
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