Induction of FOS expression by acute immobilization stress is reduced in locus coeruleus and medial amygdala of Wistar–Kyoto rats compared to Sprague–Dawley rats

Abstract

Activation of the brain noradrenergic system during acute stress is thought to play an important integrative function in coping and stress adaptation by facilitating transmission in many brain regions involved in regulating behavioral and physiologic components of the stress response. Compared with outbred control Sprague–Dawley (SD) rats, inbred Wistar–Kyoto (WKY) rats exhibit an exaggerated hypothalamic–pituitary–adrenal (HPA) response as well as increased susceptibility to certain forms of stress-related pathology. However, we have also shown previously that WKY rats exhibit reduced anxiety-like behavioral reactivity to acute stress, associated with reduced activation of the brain noradrenergic system. Thus, to understand better the possible neurobiological mechanisms underlying dysregulation of the stress response in WKY rats, we investigated potential strain differences in stress-induced neuronal activation in brain regions that are both involved in regulating behavioral and neuroendocrine stress responses, and are related to the noradrenergic system, either as targets of noradrenergic modulation or as sources of afferent innervation of noradrenergic neurons. This was accomplished by visualizing stress-induced expression of Fos immunoreactivity in the paraventricular nucleus of the hypothalamus, lateral bed nucleus of the stria terminalis, central nucleus of the amygdala, and medial nucleus of the amygdala (MeA), as well as the noradrenergic nucleus locus coeruleus (LC). Stress-induced Fos expression was found to be decreased in the LC and MeA of WKY rats compared with similarly stressed SD rats, whereas no strain differences were observed in any of the other brain regions. This suggests that strain-related differences in activation of the MeA may be involved in the abnormal neuroendocrine and behavioral stress responses exhibited by WKY rats. Moreover, as the MeA is both an afferent as well as an efferent target of the brainstem noradrenergic system, reduced MeA activation may either be a source of reduced noradrenergic reactivity seen in WKY rats, or possibly a consequence. Nonetheless, understanding the mechanisms underlying altered stress reactivity in models such as the WKY rat may contribute to a better understanding of stress-related psychopathologies such as depression, post-traumatic stress disorder or other anxiety disorders.