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Franklin M, Hlavacova N, Babic S, et al. Aldosterone Signals the Onset of Depressive Behaviour in a Female Rat Model of Depression along with SSRI Treatment Resistance. Neuroendocrinology. 2015;102(4):274-287doi: 10.1159/000431152.
Franklin, M., Hlavacova, N., Babic, S., Pokusa, M., Bermudez, I., & Jezova, D. (2015). Aldosterone Signals the Onset of Depressive Behaviour in a Female Rat Model of Depression along with SSRI Treatment Resistance. Neuroendocrinology, 102(4), 274-287. https://doi.org/10.1159/000431152
Franklin, Michael, et al. "Aldosterone Signals the Onset of Depressive Behaviour in a Female Rat Model of Depression along with SSRI Treatment Resistance." Neuroendocrinology vol. 102,4 (2015): 274-287. doi: https://doi.org/10.1159/000431152
Franklin M, Hlavacova N, Babic S, Pokusa M, Bermudez I, Jezova D. Aldosterone Signals the Onset of Depressive Behaviour in a Female Rat Model of Depression along with SSRI Treatment Resistance. Neuroendocrinology. 2015;102(4):274-287. doi: 10.1159/000431152. Epub 2015 May 09. PMID: 25968351.
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Neuroendocrinology. 2015;102(4):274-287. doi: 10.1159/000431152. Epub 2015 May 09.

Aldosterone Signals the Onset of Depressive Behaviour in a Female Rat Model of Depression along with SSRI Treatment Resistance.

Neuroendocrinology

Michael Franklin, Natasa Hlavacova, Stanislav Babic, Michal Pokusa, Isabel Bermudez, Daniela Jezova

Affiliations

  1. School of Life Sciences, Oxford Brookes University, Oxford, UK.

PMID: 25968351 DOI: 10.1159/000431152

Abstract

Depression is a serious condition that occurs more frequently in women and is often associated with treatment resistance. The main hypotheses of this study are that (a) aldosterone is an early marker of depression onset and (b) a tryptophan (TRP) depletion model of depression previously validated in male rats is treatment resistant in females. To explore possible underlying mechanisms, we have focused on factors shown to be altered in patients with treatment-resistant depression. Female Sprague-Dawley rats were treated with a control or low-TRP-containing diet for various time periods up to 21 days. The results show that aldosterone secretion increased after 4 days of TRP depletion and prior to corticosterone. Optimal effects of TRP depletion occurred at 14 days. In addition to neurochemical and behavioural changes observed previously in males, TRP depletion in females was associated with a significant decline in serum magnesium concentrations, increased serum interleukin-6, enhanced gene expression of orexin A in the frontal cortex and induced a rise in N-methyl-D-aspartate (NMDA) receptor Bmax in the amygdala. Depression-like behaviour, NMDA receptor upregulation, enhancement of the kynurenine-to-kynurenic acid ratio and magnesium were resistant to paroxetine treatment (10 mg/kg/day in drinking water for 14 days). In conclusion, aldosterone may represent an important early marker for the onset of depression-like behaviour. With respect to treatment resistance, the underlying mechanisms may involve pro-inflammatory cytokines, the kynurenine pathway, magnesium, glutamate neurotransmission and the orexin pathway. This model of treatment-resistant depression may be useful for the future development of new compounds with novel antidepressant properties.

© 2015 S. Karger AG, Basel.

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