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

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Balsevich,  Georgia
Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;

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Namendorf,  Christian
Max Planck Institute of Psychiatry, Max Planck Society;

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Gerlach,  Tamara
Max Planck Institute of Psychiatry, Max Planck Society;

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Uhr,  Manfred
Max Planck Institute of Psychiatry, Max Planck Society;

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Schmidt,  Mathias V.
Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society;

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Citation

Balsevich, G., Namendorf, C., Gerlach, T., Uhr, M., & Schmidt, M. V. (2015). The bio-distribution of the antidepressant clomipramine is modulated by chronic stress in mice: effects on behavior. FRONTIERS IN BEHAVIORAL NEUROSCIENCE, 8: 445. doi:10.3389/fnbeh.2014.00445.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0029-0326-F
Abstract
Major depression (MD) 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 (CSDS). 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.