Multifaceted strain-specific effects in a mouse model of depression and of antidepressant reversal |
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Authors: | Ibarguen-Vargas Yadira Surget Alexandre Touma Chadi Palme Rupert Belzung Catherine |
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Institution: | aU930 FRE CNRS 2448, Inserm, Tours, France;bFaculté des Sciences et Techniques, Université François Rabelais, Bât O Parc de Grandmont, 37200 Tours, France;cDepartment of Behavioral Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany;dInstitute of Biochemistry, Department of Natural Sciences, University of Veterinary Medicine, Vienna, Austria |
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Abstract: | Etiopathogenesis of depression and the cause of insensitivity to treatment remain poorly understood, although genetic makeup has been established as a contributing factor. The isogenicity of inbred mouse strains provides a useful tool for investigating the link between genes and behavior or drug response. Hence, our aim was to identify inbred mouse strains (among A/J, BALB/c, C3H, C57BL/6, CBA, DBA and FVB) sensitive to a 9-week period of unpredictable chronic mild stress (UCMS) and, from the fifth week onward, to the reversal effect of an antidepressant (AD) (imipramine, 20 mg/kg/day i.p.) on various depression-related changes: physical, behavioral and neuroendocrine states. UCMS induced a significant deterioration of the coat state (in all the strains), blunted emotional reactivity in the novelty-suppressed feeding (NSF) test (A/J, BALB/c, C57BL/6), and changes in the level of fecal corticosterone metabolites (BALB/c, C57BL/6, DBA, FVB). Imipramine treatment reversed the UCMS-induced alterations of the coat state (BALB/c, DBA), in the NSF test (A/J, BALB/c, C57BL/6) and in fecal corticosterone metabolites (BALB/c, C57BL/6). C3H, CBA and FVB mice were irresponsive to imipramine treatment. It is noteworthy that UCMS-induced physical or behavioral changes occurred without hypothalamo–pituitary–adrenal (HPA) axis alterations in some strains (A/J, C3H, CBA), although the AD-induced reversal of these changes in BALB/c and C57BL/6 was associated with HPA axis normalization. Finally, UCMS is shown to discriminate various alterations and to replicate in a strain-dependent manner diverse profiles reminiscent of human disease subtypes. UCMS may thus enable the selection of strains suitable for investigating specific depression-related features and could be an appropriate model for identifying genetic factors associated with increased vulnerability, specific symptoms of affective disorders, and AD resistance. |
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Keywords: | Inbred mouse strains Unpredictable chronic mild stress Imipramine Corticosterone HPA axis Novelty-suppressed feeding |
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