Modulation of noradrenergic signalling reverses stress-induced changes in the hippocampus: involvement of orexinergic systems

Stress can be beneficial for adapting to dangerous situations in the short term, but can be damaging in the long term, especially in the hippocampus. The noradrenergic and orexinergic systems play important roles in the stress response. This study investigated the effect of noradrenergic activation on the changes induced by chronic stress in the hippocampus and the involvement of orexinergic modulation in this process. Twenty male Wistar rats were subjected to chronic stress, acute stress, administration of α2 receptor antagonist yohimbine, or their combinations. Plasma corticosterone (CORT) was measured using a fluorometric method. Expression of prepro-orexin (prepro-OX), orexin receptor-1 (OXr1), and glucocorticoid receptor (GR) was analyzed using RT-PCR. Neuronal populations were quantified using Nissl staining. Chronic and acute stress increased plasma CORT levels, gene expression of prepro-OX, OXr1, and GR, while decreasing neuronal number, with the chronic stress having a more pronounced effect. The stress- induced and Yohimbine treated groups demonstrated a higher level of plasma CORT. Chronic stress substantially increased prepro-OX expression, while yohimbine recovered the profile in chronically stressed animals. OXr1 expression was profoundly higher in the chronic stress group, while chronic stress combined with yohimbine decreased that profile. Similarly, chronic stress upregulated glucocorticoid receptor, while chronic stress combined with yohimbine reversed the effect. Conversely, the chronic stress reduced hippocampal neuronal populations and chronic stress combined with yohimbine partially compensated the neuronal numbers compared to chronic stress alone. The results suggest that noradrenergic signalling can reverse the chronic stress-induced impairments in prepro-OX, OXr1, GR, and neuronal population.