Fluoxetine impacts hypothalamic-pituitary-adrenal axis regulation and changes stress-coping behaviour in mice selectively bred for extremes in stress reactivity

• Published in: Pharmacopsychiatry
• Main Authors: Heinzmann, JM, Knapman, A, van Nieuwenhuijzen, P, Tietze, L, Touma, C
• Format: Conference Proceeding
• Language: English
• Published: 29.09.2011
• ISSN: 0176-3679; 1439-0795
• DOI: 10.1055/s-0031-1292495

An aberrant regulation of the stress hormone system is frequently observed in patients suffering from major depression and this dysregulation is amendable by antidepressant treatment. Applying a translational approach, we used an animal model mimicking this dysregulation of the HPA axis. The model consists of three independent mouse lines selectively bred for high (HR), intermediate (IR) or low (LR) corticosterone (CORT) secretion in response to stressors. We investigated the impact of chronic fluoxetine (Flx) treatment on HPA axis function and emotional behaviour. After 35 d of Flx treatment, HR and IR mice showed a stronger suppression of plasma CORT in response to Dex in the Dex/CRH test compared to the vehicle group. However, no Flx-induced difference in CRH-triggered CORT secretion was detected in these two lines. In LR animals both, the treatment and vehicle group showed a strong suppression of plasma CORT after Dex. However, the CRH-triggered CORT secretion was significantly decreased in Flx-treated LR mice. Regarding their emotional behaviour, a significant increase in passive stress-coping of HR and IR mice was observed, i.e. they showed increased floating in the FST. Our results indicate that HPA axis regulation as well as behavioural stress responsiveness is modified by the Flx treatment. The molecular mechanisms underlying these effects likely involve the GR-mediated feedback of the HPA axis and the brain CRH system, both of which are currently under investigation.