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

• Published in: Pharmacogenetics and genomics Vol. 21; no. 12; pp. 779 - 789
• Main Authors: Binder, Elke, Malki, Karim, Paya-Cano, Jose L, Fernandes, Cathy, Aitchison, Katherine J, Mathé, Aleksander A, Sluyter, Frans, Schalkwyk, Leonard C
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins, Inc 01-12-2011; Lippincott Williams & Wilkins
• Subjects: Adult and adolescent clinical studies; Animals; Antidepressive Agents - pharmacology; Biological and medical sciences; Citalopram - pharmacology; Depression; Female; General pharmacology; Genotype; Male; Maternal Deprivation; Medical sciences; Medicin och hälsovetenskap; Mice; Mice, Inbred Strains; Mood disorders; Nortriptyline - pharmacology; Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions; Pharmacology. Drug treatments; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Social Environment; Stress, Psychological - drug therapy; Stress, Psychological - genetics; Stress, Psychological - psychology; Mood disorder; Drug; maternal separation; Nortriptyline; Therapeutic Drugs for Depression; Pharmacogenetics; maternal deprivation; Depressions; Escitalopram; Psychotropic; Rodentia; Depression; antidepressants; Stress; Strain; Genome-based; Vertebrata; Mammalia; Mouse; Antidepressant agent; Early; Inbred; Genome
• ISSN: 1744-6872; 1744-6880; 1744-6880
• DOI: 10.1097/FPC.0b013e32834b3f35

RATIONALESelecting 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.
OBJECTIVESMouse 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.
METHODOur 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.
RESULTSDespite 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.
CONCLUSIONA 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.