Chronic Corticosterone Administration Induced Affective Disturbances, but Did Not Alter Consolidated Active Avoidance...

Stress is a major risk factor for various psychiatric disorders. Activation of the hypothalamic-pituitary-adrenal (HPA) axis increases cortisol release, whereas prolonged glucocorticoid exposure has been linked to cognitive impairment and mood disorders. In this study, we examined whether chronic corticosterone administration alters emotional states, active coping strategies, and associated neuronal activation in rats. Male Long-Evans rats were trained in a lever-press task to avoid signaled foot shocks and then assigned into control (CON) or corticosterone-treated (CORT) groups, with the latter receiving daily corticosterone injections for 21 consecutive days. Afterward, emotional states were assessed using the elevated plus maze (EPM), forced swim test (FST), and sucrose preference test (SPT). Finally, the animals were re-tested for their active avoidance behavior, while neuronal activation levels in related brain areas were evaluated. Our results showed that chronic corticosterone administration led to decrease in body weight and deteriorated fur condition over time. The stressed rats showed hypolocomotion in EPM but no changes in anxiety-like behavior, increased despair-like behavior in FST, and developed anhedonia in SPT. Despite these emotional alterations, active avoidance performance and freezing behavior were not affected. Consistently, analyses of numbers of c-Fos positive neurons in the prelimbic cortex (PL), infralimbic cortex (IL), nucleus accumbens core (NAcc), nucleus accumbens shell (NAcs), dorsal CA3 (dCA3), and basolateral amygdala (BLA), did not differ between groups. Together, our results suggested that chronic corticosterone administration induced physical deterioration. These animals were less active, developed behavioral despair and anhedonia, but did not alter their coping strategies to threat-related signals.Significance Statement Chronic stress is strongly associated with affective disorders, yet previous studies have reported mixed findings on how it affects avoidance and coping behaviors. Using a chronic corticosterone administration model in rats, we demonstrated that sustained corticosterone elevation induced physiological deterioration, hypolocomotion, despair-like behavior, and anhedonia. However, well-established active avoidance behavior, along with neuronal activation levels in key cortico-limbic regions, were not affected. These findings revealed a dissociation between stress-induced affective disturbances and preserved instrumental coping execution. Our results suggested that chronic corticosterone exposure may preferentially disrupt emotional processing while sparing consolidated avoidance networks, refining current understanding of how chronic stress differentially affects affective and action control systems.