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Antidepressants and the resilience to early-life stress in inbred mouse strains

Binder, Elke and Malki, Karim and Paya-Cano, Jose L and Fernandes, Cathy and Aitchison, Katherine J and Mathé, Aleksander A and Sluyter, Frans and Schalkwyk, Leonard C (2011) 'Antidepressants and the resilience to early-life stress in inbred mouse strains.' Pharmacogenetics and Genomics, 21 (12). pp. 779-789. ISSN 1744-6872

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Abstract

Rationale: Selecting an effective treatment for patients with major depressive disorder is a perpetual problem for psychiatrists. It is of particular interest to explore the interaction between genetic predisposition and environmental factors. Objectives: Mouse inbred strains vary in baseline performance in depression-related behaviour tests, which were originally validated as tests of antidepressant response. Therefore, we investigated interactions between environmental stress, genotype, and drug response in a multifactorial behaviour study. METHOD: Our study design included four inbred mouse strains (129S1/SvlmJ, C57LB/6J, DBA/2J and FVB/NJ) of both sexes, two subjected to environmental manipulations (maternal separation and unpredictable chronic mild stress) and two representative of treatment with antidepressants (escitalopram and nortryptiline vs. vehicle). The mice treated with antidepressants were further divided into those administered acute (1 day) and subchronic (14 days) regimes, giving 144 experimental groups in all, each with at least seven animals. All animals were tested using the Porsolt forced-swim test (FST) and the hole-board test. Results: Despite a 24-h maternal separation (MS) or a 14-day unpredictable chronic mild stress protocol, most animals seemed to be resilient to the stress induced. One compelling finding is the long-lasting, strain-specific effect of MS resulting in an increased depression-like behaviour in the Porsolt FST and elevated anxiety-related behaviour in the hole-board test seen in 129S1/SvImJ mice. Nortriptyline was effective in reversing the effect of MS in the FST in 129S1/SvlmJ male mice. Conclusion: A single 24-h maternal separation of pups from their mother on postnatal day 9 is a sufficient insult to result in a depression-like phenotype in adult 129S1/SvImJ mice but not in C57LB/6 J, DBA/2 J, and FVB/NJ mice. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Item Type: Article
Uncontrolled Keywords: antidepressants; depression; escitalopram; Genome-based Therapeutic Drugs for Depression; maternal deprivation; maternal separation; nortriptyline; pharmacogenetics
Subjects: Q Science > QH Natural history > QH426 Genetics
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 11 Nov 2014 13:36
Last Modified: 15 Jan 2022 00:42
URI: http://repository.essex.ac.uk/id/eprint/10983

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