Involvement of the hypothalamic-pituitary-adrenal axis in the antidepressant-like effects of mild hypoxic preconditioning in rats

Rybnikova, Elena; Mironova, Vera; Pivina, Svetlana; Tulkova, Ekaterina; Ordyan, Natalia; Nalivaeva, Natalia; Turner, Anthony; Samoilov, Michail

doi:10.1016/j.psyneuen.2007.05.010

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Volume 32, Issue 7 , Pages 813-823, August 2007

Involvement of the hypothalamic-pituitary-adrenal axis in the antidepressant-like effects of mild hypoxic preconditioning in rats

Elena Rybnikova
- Laboratory of Neuroendocrinology, Pavlov Institute of Physiology, Russian Academy of Sciences, Makarova 6, 199034 St. Petersburg, Russian Federation
- Corresponding author. Tel.: +78137072535; fax: +78123280501.
Vera Mironova
- Laboratory of Neuroendocrinology, Pavlov Institute of Physiology, Russian Academy of Sciences, Makarova 6, 199034 St. Petersburg, Russian Federation
Svetlana Pivina
- Laboratory of Neuroendocrinology, Pavlov Institute of Physiology, Russian Academy of Sciences, Makarova 6, 199034 St. Petersburg, Russian Federation
Ekaterina Tulkova
- Laboratory of Regulation of Brain Neuron Functions, Pavlov Institute of Physiology, Russian Academy of Sciences, 199034 St. Petersburg, Russian Federation
Natalia Ordyan
- Laboratory of Neuroendocrinology, Pavlov Institute of Physiology, Russian Academy of Sciences, Makarova 6, 199034 St. Petersburg, Russian Federation
Natalia Nalivaeva
- Institute of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK
Anthony Turner
- Institute of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK
Michail Samoilov
- Laboratory of Regulation of Brain Neuron Functions, Pavlov Institute of Physiology, Russian Academy of Sciences, 199034 St. Petersburg, Russian Federation

Received 15 April 2007; received in revised form 19 April 2007; accepted 21 May 2007.

Summary

The preconditioning (PC) by using mild intermittent hypobaric hypoxia (PC) increases a resistance of the brain to severe hypoxia/ischemia and various stresses. Recently, potent antidepressant-like effects of PC have been described in animal models of depression. In the present study, the impact of PC on the activity and feedback regulation of the hypothalamic-pituitary-adrenal axis (HPA) impaired in depression has been studied in the model of shock-induced depression in rats. PC completely prevented depressive-like behavior (54% reduction in ambulance, 59% reduction in rearing in the open field, 654% increase of the anxiety level in the elevated plus maze), the HPA hyperactivity and the impairment of HPA feedback regulation that appeared in response to the inescapable footshock. Not affecting basal HPA activity, PC remarkably enhanced the HPA reactivity to stresses and substantially up-regulated the expression of glucocorticoid receptors in the ventral hippocampus following footshock that apparently contributes to the mechanisms responsible for the antidepressant-like action of PC.

Keywords: Depression, Hypoxic preconditioning, Antidepressant-like effects, Hypothalamic-pituitary-adrenal axis, Glucocorticoid receptors