Mouse strain differences in SSRI sensitivity correlate with serotonin transporter binding and function

Abstract Selective serotonin reuptake inhibitors (SSRIs) bind 5-HT transporters, leading to the accumulation of 5-HT and amelioration of depression. Although different mouse strains show varying sensitivity to SSRIs in mouse models of depression, the underlying mechanism of these strain differences...

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Autores principales:	Zeng-liang Jin, Xiao-Fei Chen, Yu-hua Ran, Xiao-rong Li, Jie Xiong, Yuan-yuan Zheng, Na-na Gao, Yun-Feng Li
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/78bdd53ea6f84db08c81c21dfa765df5
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spelling	oai:doaj.org-article:78bdd53ea6f84db08c81c21dfa765df52021-12-02T15:05:12ZMouse strain differences in SSRI sensitivity correlate with serotonin transporter binding and function10.1038/s41598-017-08953-42045-2322https://doaj.org/article/78bdd53ea6f84db08c81c21dfa765df52017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08953-4https://doaj.org/toc/2045-2322Abstract Selective serotonin reuptake inhibitors (SSRIs) bind 5-HT transporters, leading to the accumulation of 5-HT and amelioration of depression. Although different mouse strains show varying sensitivity to SSRIs in mouse models of depression, the underlying mechanism of these strain differences remains unclear. Here, the SSRI citalopram dose-dependently reduced immobility time in both the FST and TST in DBA/2J mice but not C57BL/6J mice, whereas fluoxetine showed the opposite results. Paroxetine similarly reduced immobility time in both strains. The affinity of citalopram for the 5-HT transporter was 700-fold higher in DBA/2J mice than in C57BL/6J mice, whereas the affinity of fluoxetine was 100-fold higher in C57BL/6J mice than in DBA/2J mice. Furthermore, high citalopram concentrations were required for [3H]5-HT uptake in C57BL/6J but not in DBA/2J mouse cortical synaptosomes, whereas fluoxetine showed the opposite results. The effects of paroxetine on 5-HT transporter binding and synaptosomal 5-HT uptake were similar in the two strains. These results suggest that immobility duration depends on 5-HT transporter binding levels, which lead to apparent strain differences in immobility time in the FST and TST. Furthermore, differences in 5-HT transporter binding may cause variations in SSRI effects on behaviors.Zeng-liang JinXiao-Fei ChenYu-hua RanXiao-rong LiJie XiongYuan-yuan ZhengNa-na GaoYun-Feng LiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Zeng-liang Jin Xiao-Fei Chen Yu-hua Ran Xiao-rong Li Jie Xiong Yuan-yuan Zheng Na-na Gao Yun-Feng Li Mouse strain differences in SSRI sensitivity correlate with serotonin transporter binding and function
description	Abstract Selective serotonin reuptake inhibitors (SSRIs) bind 5-HT transporters, leading to the accumulation of 5-HT and amelioration of depression. Although different mouse strains show varying sensitivity to SSRIs in mouse models of depression, the underlying mechanism of these strain differences remains unclear. Here, the SSRI citalopram dose-dependently reduced immobility time in both the FST and TST in DBA/2J mice but not C57BL/6J mice, whereas fluoxetine showed the opposite results. Paroxetine similarly reduced immobility time in both strains. The affinity of citalopram for the 5-HT transporter was 700-fold higher in DBA/2J mice than in C57BL/6J mice, whereas the affinity of fluoxetine was 100-fold higher in C57BL/6J mice than in DBA/2J mice. Furthermore, high citalopram concentrations were required for [3H]5-HT uptake in C57BL/6J but not in DBA/2J mouse cortical synaptosomes, whereas fluoxetine showed the opposite results. The effects of paroxetine on 5-HT transporter binding and synaptosomal 5-HT uptake were similar in the two strains. These results suggest that immobility duration depends on 5-HT transporter binding levels, which lead to apparent strain differences in immobility time in the FST and TST. Furthermore, differences in 5-HT transporter binding may cause variations in SSRI effects on behaviors.
format	article
author	Zeng-liang Jin Xiao-Fei Chen Yu-hua Ran Xiao-rong Li Jie Xiong Yuan-yuan Zheng Na-na Gao Yun-Feng Li
author_facet	Zeng-liang Jin Xiao-Fei Chen Yu-hua Ran Xiao-rong Li Jie Xiong Yuan-yuan Zheng Na-na Gao Yun-Feng Li
author_sort	Zeng-liang Jin
title	Mouse strain differences in SSRI sensitivity correlate with serotonin transporter binding and function
title_short	Mouse strain differences in SSRI sensitivity correlate with serotonin transporter binding and function
title_full	Mouse strain differences in SSRI sensitivity correlate with serotonin transporter binding and function
title_fullStr	Mouse strain differences in SSRI sensitivity correlate with serotonin transporter binding and function
title_full_unstemmed	Mouse strain differences in SSRI sensitivity correlate with serotonin transporter binding and function
title_sort	mouse strain differences in ssri sensitivity correlate with serotonin transporter binding and function
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/78bdd53ea6f84db08c81c21dfa765df5
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Mouse strain differences in SSRI sensitivity correlate with serotonin transporter binding and function

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