Role of noradrenergic projections to the bed nucleus of the stria terminalis in the regulation of the hypothalamic–pituitary–adrenal axis

The bed nucleus of the stria terminalis (BNST) plays an important role in the regulation of the hypothalamic–pituitary–adrenal (HPA) axis during stress and it is a major extrahypothalamic relay to the paraventricular nucleus of the hypothalamus (PVN) from the amygdala and the hippocampus. In this review, we discuss the anatomical, neurochemical and behavioral evidence that substantiate a role for noradrenergic terminals of the anterior BNST in the regulation of the HPA axis. We propose the hypothesis that BNST noradrenaline (NA) participates in the regulation of the hippocampal inhibitory influence on the HPA axis activation. The observation that NA exerts a tonic inhibitory effect upon glutamatergic transmission in the anterior BNST supports this hypothesis. We also discuss the known mechanisms involved in the regulation of BNST NA extracellular levels and the possible interactions between NA and corticotropin-releasing hormone (CRH), and of CRH with glutamate (GLU) in the regulation of the HPA axis activity exerted by the BNST. The evidence discussed in the present review situates the BNST as a key extrahypothalamic center that relays and integrates limbic and autonomic information related to stress responses suggesting that dysregulation in the functioning of the BNST may underlie the pathophysiology of stress-related psychiatric disorders.