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5‐HT depletion, but not 5‐HT1A antagonist, prevents the anxiolytic‐like effect of citalopram in rat contextual conditioned fear stress model

Published online by Cambridge University Press:  21 February 2013

Takahiro Masuda ,
Hiroyuki Nishikawa ,
Takeshi Inoue ,
Hiroyuki Toda ,
Shin Nakagawa ,
Shuken Boku  and
Tsukasa Koyama
Takahiro Masuda
Affiliation:
Department of Psychiatry, Hokkaido University Graduate School of Medicine, Kita‐ku, Sapporo, Japan
Hiroyuki Nishikawa
Affiliation:
Department of Psychiatry, Hokkaido University Graduate School of Medicine, Kita‐ku, Sapporo, Japan
Takeshi Inoue*
Affiliation:
Department of Psychiatry, Hokkaido University Graduate School of Medicine, Kita‐ku, Sapporo, Japan
Hiroyuki Toda
Affiliation:
Department of Psychiatry, Hokkaido University Graduate School of Medicine, Kita‐ku, Sapporo, Japan
Shin Nakagawa
Affiliation:
Department of Psychiatry, Hokkaido University Graduate School of Medicine, Kita‐ku, Sapporo, Japan
Shuken Boku
Affiliation:
Department of Psychiatry, Hokkaido University Graduate School of Medicine, Kita‐ku, Sapporo, Japan
Tsukasa Koyama
Affiliation:
Department of Psychiatry, Hokkaido University Graduate School of Medicine, Kita‐ku, Sapporo, Japan
*
Takeshi Inoue, Department of Psychiatry, Hokkaido University Graduate School of Medicine, North 15, West 7, Sapporo 060–8638, Japan. Tel: +81‐11‐706‐5160; Fax: +81‐11‐706‐5081; E‐mail: tinoue@med.hokudai.ac.jp
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Abstract

Objective

Selective serotonin reuptake inhibitors (SSRIs) have been widely used in the treatment of most anxiety disorders. In this study, to clarify the mechanism of the anxiolytic effect, we investigated the mechanism underlying the effect of the SSRI citalopram on rat contextual conditioned fear stress (CFS), an animal model of anxiety.

Methods

Rats individually received footshocks in a shock chamber. More than 1 day later, they were given citalopram and/or dl‐p‐chlorophenylalanine (PCPA), various subtype‐selective serotonin (5‐HT) receptor antagonists: the 5‐HT1A receptor antagonist WAY 100635, the 5‐HT2A receptor antagonist MDL 100907, the 5‐HT2C receptor antagonist SB 242084, the 5‐HT3 receptor antagonist tropisetron, the 5‐HT4 receptor antagonist GR 125487, the 5‐HT6 receptor antagonist SB 258585 or the 5‐HT7 receptor antagonist SB 269970. After drug administration, freezing behaviour, which was used as an index of anxiety, was analysed in the same shock chamber without shocks.

Results

Citalopram dose dependently reduced conditioned freezing behaviour. The anxiolytic‐like effect of citalopram was prevented completely by pretreatment with the 5‐HT‐depleting agent PCPA, but not by the 5‐HT1A receptor antagonist WAY 100635. Furthermore, none of the subtype‐selective 5‐HT receptor antagonists significantly affected conditioned freezing or affected the anxiolytic‐like effect of citalopram.

Conclusion

The anxiolytic‐like effect of citalopram in contextual CFS model depends on 5‐HT availability. In addition, contextual CFS model is suggested to be completely different from conventional anxiety models in neural mechanism or manners of serotonergic involvement. However, further studies are needed to identify the pharmacological mechanisms responsible for the anxiolytic‐like effect of citalopram.

Keywords

5‐HT1A receptoranxietyconditioned feardl‐p‐chlorophenylalanineselective serotonin reuptake inhibitor
Type
Original Articles
Information
Acta Neuropsychiatrica , Volume 25 , Issue 2 , April 2013 , pp. 77 - 84
Copyright
Copyright © Scandinavian College of Neuropsychopharmacology 2013

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