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The bio-distribution of the antidepressant clomipramine is modulated by chronic stress in mice: Effects on behavior

By Georgia eBalsevich, Christian eNamendorf, Tamara eGerlach, Manfred eUhr and Mathias V. Schmidt


Major depression is one of the most common psychiatric disorders, severely affecting the quality of life of millions of people worldwide. Despite the availability of several classes of antidepressants, treatment efficacy is still very variable and many patients do not respond to the treatment. Clomipramine (CMI), a classical and widely used antidepressant, shows widespread interindividual variability of efficacy, while the environmental factors contributing to such variability remain unclear. We investigated whether chronic stress modulates the bio-distribution of CMI, and as a result the behavioral response to CMI treatment in a mouse model of chronic social defeat stress. Our results show that stress exposure increased anxiety-like and depressive-like behaviors and altered the stress response. Chronic defeat stress furthermore significantly altered CMI bio-distribution. Interestingly, CMI bio-distribution highly correlated with anxiety-like and depressive-like behaviors only under basal conditions. Taken together, we provide first evidence demonstrating that chronic stress exposure modulates CMI bio-distribution and behavioral responses. This may contribute to CMI’s broad interindividual variability, and is especially relevant in clinical practice

Topics: Clomipramine, Tissue Distribution, mouse model, Antidepressants, chronic social defeat stress, Metabolic ratio, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Publisher: Frontiers Media S.A.
Year: 2015
DOI identifier: 10.3389/fnbeh.2014.00445
OAI identifier: oai:doaj.org/article:3729fd56f672435dad8319f7db3de471
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