Effect of inescapable stress in rodent models of depression and posttraumatic stress disorder on CRH and vasopressin immunoreactivity in the hypothalamic paraventricular nucleus.

The present study was designed to reveal possible common and specific neuroendocrine mechanisms of depression and anxiety-like states in rodents. Animal models of depression and anxiety (in particular, posttraumatic stress disorder, PTSD) were applied including the learned helplessness and the stress-restress paradigms, respectively. Immunocytochemical staining revealed that depressive- and anxiety-like states in animals were accompanied by the rise in corticotropin-releasing hormone (CRH) immunoreactivity in the parvocellular division of the hypothalamic paraventricular nucleus (PVN). Decrease in vasopressin-immunoreactivity in early period of depressive-like state development was followed by the normalization of vasopressin content in the hypothalamic PVN in delayed period. Increased CRH and vasopressin immunoreactivity in the magnocellular part of the PVN in delayed period of anxiety-like state development was detected only in the stress-restress paradigm. These results suggest that CRH hyperdrive in the parvocellular PVN appears to be a common neuroendocrine abnormality for depressive- and anxiety-like states in animals, while over-expression of CRH and vasopressin in the magnocellular PVN represents a specific feature of anxiety/PTSD-like state.

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

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.

Antidepressant-like effects of mild hypoxia preconditioning in the learned helplessness model in rats.

The effects of preconditioning using mild repetitive hypobaric hypoxia (360 Torr for 2 h each of 3 days) have been studied in the learned helplessness model of depression in rats. Male Wistar rats displayed persistent depressive symptoms (depressive-like behaviour in open field, increased anxiety levels in elevated plus maze, ahedonia, elevated plasma glucocorticoids and impaired dexamethasone test) following the exposure to unpredictable and inescapable footshock in the learned helplessness paradigm. Antidepressant treatment (ludiomil, 5 mg/kg i.p.) augmented the development of the depressive state. The hypoxic preconditioning had a clear antidepressive action returning the behavioural and hormonal parameters to the control values and was equally effective in terms of our study as the antidepressant. The findings suggest hypoxic preconditioning as an effective tool for the prophylaxis of post-stress affective pathologies in humans.