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 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 footshocks and then assigned into control or corticosterone-treated 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 retested 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, infralimbic cortex, nucleus accumbens core, nucleus accumbens shell, dorsal CA3, and basolateral amygdala did not differ between groups. Together, our results suggested that chronic corticosterone administration induced physical deterioration. These animals were less active and developed behavioral despair and anhedonia, but did not alter their coping strategies to threat-related signals.