Abstract
Background: Sleep fragmentation, a hallmark of obstructive sleep apnea (OSA), has been linked to mood disorders through disrupted neuroendocrine regulation. However, the time-dependent development of depression-like behaviors and hormonal changes following recurrent sleep fragmentation remains unclear. This study examined the effects of repeated experimental sleep fragmentation on depression-like behavior and endocrine status in male Wistar rats. Methods: Twenty-four male Wistar rats were randomly assigned to three experimental groups (n = 8 per group): treadmill control (TC; stationary treadmill), activity control (AC; 10-min running/30-min resting cycles), and sleep fragmentation (SF; 30-s running/90-s resting cycles). Treatments were applied daily for 14 consecutive days during the first 6 h of the light phase. Depression-like behavior was assessed via the forced swimming test on days 1, 7, and 14. Body weight was monitored throughout, and serum corticosterone and testosterone were measured at the endpoint. Sleep architecture was inferred from the treadmill protocol rather than directly recorded. Results: SF rats showed progressive increases in immobility and decreases in swimming and climbing over 14 days, reflecting the gradual emergence of depression-like behavior. SF animals also exhibited significantly reduced body-weight gain, elevated corticosterone (p < 0.01), and reduced testosterone (p < 0.001) compared with controls. Conclusions: Subchronic sleep fragmentation induced a progressive depression-like phenotype accompanied by neuroendocrine alterations, suggesting that recurrent sleep interruptions relevant to OSA may contribute to depression-associated endocrine dysregulation. Because sleep architecture was not directly recorded and hormones were measured only at the endpoint, these findings should be interpreted as associative rather than mechanistic.