Abstract
The hippocampus is sensitive to high levels of glucocorticoids. During stress response, it suffers biochemical and cellular changes that affect functions such as spatial memory and exploratory behavior. In this study, we analyzed the influence of the neurosteroid progesterone (PROG), on stress-induced changes in urinary corticosterone (CORT) levels, spatial memory and exploratory behavior. Castrated adult male rats were implanted with PROG or vehicle (VEHI), and then exposed to chronic stress by overcrowding or ultrasonic noise for ten days. PROG and CORT levels were assessed in urine using high-performance liquid chromatography (HPLC). Implanted PROG inhibited stress-induced CORT raise, prevented spatial memory impairment in the Morris water maze, and eliminated increased exploratory behavior in the hole-board test. These results suggest protective effects of PROG against the corticosteroids raise and behavioral deficit generated by both stressful situations, possibly mediated by its anxiolytic mechanisms.
Highlights
It has been shown that stress stimulates the hypothalamus-pituitary-adrenal (HPA) axis increasing the blood levels of circulating glucocorticoids (GCs), especially after prolonged exposure (McEwen, 2000)
We used high-performance liquid chromatography (HPLC) to measure the quantity of urinary progesterone released after insertion of the subcutaneous implant
The effect of progesterone vs. vehicle sub-dermic implants on chronic-stress consequences was assessed in Wistar rats
Summary
It has been shown that stress stimulates the hypothalamus-pituitary-adrenal (HPA) axis increasing the blood levels of circulating glucocorticoids (GCs), especially after prolonged exposure (McEwen, 2000). In aged oophorectomized rats, the long-term treatment with estrogen and PROG enhanced information acquisition in spatial memory tasks (Frye, Duffy & Walf, 2007), PROG can revert memory impairment caused by cortisol administration (Kuhlmann & Wolf, 2005) These results show that PROG effects on cognitive functions may not always be negative and may depend on the neurophysiologic context. Several methods have been used to generate stress in animals, social stress models are closer to human situations in which stressful stimulus normally comes from other individuals (Henry et al, 1993) These models are effective in raising GCs as consequence of HPA-axis hyperactivity, and causing neuronal alterations in the hippocampus and its associated functions. We intended to establish the possible neuroprotective influence of PROG implants on GCs levels, memory, and exploratory behavior, in rats exposed to artificial USVs or overcrowding
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