Modulatory effects of norepinephrine, acting on alpha 1 receptors in the central nucleus of the amygdala, on behavioral and neuroendocrine responses to acute immobilization stress

Abstract

The central nucleus of the amygdala (CeA) is a component of the limbic fear-anxiety circuit, and has also been implicated in regulation of the hypothalamic-pituitary-adrenal (HPA) stress axis. The CeA receives dense noradrenergic innervation, and is rich in expression of alpha(1)-adrenergic receptors. We hypothesized that norepinephrine (NE), acting on alpha(1) receptors in CeA, may modulate stress-induced anxiety-like behavioral responses and HPA activation. To investigate the role of alpha(1) adrenergic receptors in CeA on stress-induced behavioral reactivity, the alpha(1) antagonist benoxathian was microinjected bilaterally into CeA of male Sprague-Dawley rats, and anxiety-like behavioral responses to acute immobilization stress were measured on the Social Interaction (SI) test and on the Elevated Plus-maze (EPMZ). Benoxathian dose dependently blocked the reduction in SI time induced by immobilization stress, whereas beta-receptor antagonists had no effect, consistent with an absence of beta-receptors in CeA. By contrast, in separate experiments, benoxathian had no effect on stress-induced reduction in open-arm exploratory behavior on the EPMZ, nor on stress-induced plasma ACTH secretion. These results confirm that the SI test and EPMZ measure different aspects of behavioral stress reactivity that can be modulated independently, and likewise, that noradrenergic modulation of behavioral stress reactivity can occur independently of modulation of the HPA axis.