Back to Journals » Neuropsychiatric Disease and Treatment » Volume 10

Effect of the coadministration of citalopram with mirtazapine or atipamezole on rat contextual conditioned fear

Authors Masuda T, Inoue T, An Y, Takamura N, Nakagawa S, Kitaichi Y, Koyama T, Kusumi I

Received 7 October 2013

Accepted for publication 4 December 2013

Published 11 February 2014 Volume 2014:10 Pages 289—295

DOI https://doi.org/10.2147/NDT.S55507

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 6

Takahiro Masuda,1,2 Takeshi Inoue,1 Yan An,1 Naoki Takamura,1,3 Shin Nakagawa,1 Yuji Kitaichi,1 Tsukasa Koyama,1 Ichiro Kusumi1

1Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo Japan; 2Medical Affairs, Dainippon Sumitomo Pharma, Co, Ltd, Tokyo, Japan; 3Regenerative and Cellular Medicine Office, Dainippon Sumitomo Pharma, Co, Ltd, Osaka, Japan

Background: Mirtazapine, a noradrenergic and specific serotonergic antidepressant, which blocks the α2-adrenergic autoreceptors and heteroreceptors, has shown anxiolytic properties in clinical trials and preclinical animal experiments. The addition of mirtazapine to selective serotonin reuptake inhibitors (SSRIs) is clinically suggested to be more effective for anxiety disorders. In this study, we examined the combined effects of mirtazapine and citalopram, an SSRI, on the freezing behavior of rats, which was induced by contextual conditioned fear as an index of anxiety or fear.
Methods: Male Sprague Dawley rats individually received footshocks in a shock chamber, and 24 hours later, they were given citalopram and/or mirtazapine injections. One hour after citalopram and 30 minutes after mirtazapine administration, freezing behavior was analyzed in the same shock chamber without shocks.
Results: Mirtazapine decreased freezing in a dose-dependent manner, which is consistent with a previous report; it also enhanced an anxiolytic-like effect at a high dose (30 mg/kg) of citalopram. Because mirtazapine blocks α2-adrenoreceptors, the combined effect of atipamezole, a selective α2 receptor antagonist, with citalopram was also examined. Similar to mirtazapine, atipamezole reduced freezing dose-dependently, but the enhancement of citalopram's effects by atipamezole was not clear when compared with mirtazapine.
Conclusion: The present findings suggest that mirtazapine has an anxiolytic-like effect and may enhance the anxiolytic-like effect of SSRIs, but this enhancement may not be explained by its anti-α2 property alone.

Keywords: anxiety, conditioned fear, selective serotonin reuptake inhibitor, mirtazapine, α2-adrenoreceptor

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]

 

Other articles by this author:

Interpersonal sensitivity mediates the effects of child abuse and affective temperaments on depressive symptoms in the general adult population

Otsuka A, Takaesu Y, Sato M, Masuya J, Ichiki M, Kusumi I, Inoue T

Neuropsychiatric Disease and Treatment 2017, 13:2559-2568

Published Date: 5 October 2017

The influence of childhood abuse, adult life events, and affective temperaments on the well-being of the general, nonclinical adult population

Kanai Y, Takaesu Y, Nakai Y, Ichiki M, Sato M, Matsumoto Y, Ishikawa J, Ono Y, Murakoshi A, Tanabe H, Kusumi I, Inoue T

Neuropsychiatric Disease and Treatment 2016, 12:823-832

Published Date: 12 April 2016

Differences between bipolar and unipolar depression on Rorschach testing

Kimura H, Osaki A, Kawashima R, Inoue T, Nakagawa S, Suzuki K, Asakura S, Tanaka T, Kitaichi Y, Masui T, Kitagawa N, Kako Y, Abekawa T, Kusumi I, Yamanaka H, Denda K, Koyama T

Neuropsychiatric Disease and Treatment 2013, 9:619-627

Published Date: 7 May 2013

Effect of triiodothyronine (T3) augmentation of acute milnacipran administration on monoamine levels: an in vivo microdialysis study in rats

Kitaichi Y, Inoue T, Nakagawa S, Boku S, Kato A, Kusumi I, Koyama T

Neuropsychiatric Disease and Treatment 2012, 8:501-507

Published Date: 30 October 2012

Readers of this article also read:

Green synthesis of water-soluble nontoxic polymeric nanocomposites containing silver nanoparticles

Prozorova GF, Pozdnyakov AS, Kuznetsova NP, Korzhova SA, Emel’yanov AI, Ermakova TG, Fadeeva TV, Sosedova LM

International Journal of Nanomedicine 2014, 9:1883-1889

Published Date: 16 April 2014

Methacrylic-based nanogels for the pH-sensitive delivery of 5-Fluorouracil in the colon

Ashwanikumar N, Kumar NA, Nair SA, Kumar GS

International Journal of Nanomedicine 2012, 7:5769-5779

Published Date: 15 November 2012

A novel preparation method for silicone oil nanoemulsions and its application for coating hair with silicone

Hu Z, Liao M, Chen Y, Cai Y, Meng L, Liu Y, Lv N, Liu Z, Yuan W

International Journal of Nanomedicine 2012, 7:5719-5724

Published Date: 12 November 2012

Cross-linked acrylic hydrogel for the controlled delivery of hydrophobic drugs in cancer therapy

Deepa G, Thulasidasan AK, Anto RJ, Pillai JJ, Kumar GS

International Journal of Nanomedicine 2012, 7:4077-4088

Published Date: 27 July 2012

Crystallization after intravitreal ganciclovir injection

Pitipol Choopong, Nattaporn Tesavibul, Nattawut Rodanant

Clinical Ophthalmology 2010, 4:709-711

Published Date: 14 July 2010