CRH Signalling in the Bed Nucleus of the Stria Terminalis is Involved in Stress-Induced Cardiac Vagal Activation in Conscious Rats

Abstract

The bed nucleus of the stria terminalis (BNST) is involved in autonomic and behavioral reactions to fearful stimuli and contains corticotropin-releasing hormone (CRH) fibers and terminals. The role of CRH in the medial part of the BNST in the regulation of heart rate (HR) and PQ interval of theThe bed nucleus of the stria terminalis (BNST) is a rostral forebrain structure that is enclosed by the lateral ventricle, lateral septum, fornix, nucleus accumbens, preoptic area and hypothalamus. The BNST has been recognized as an important relay station which links the amygdala and hippocampus with the paraventricular hypothalamic nucleus (PVN) and brain stem regions (Herman et al. 1994;Pacak et al. 1995;Davis et al. 1997). Projections have been found from the BNST to autonomic regulatory brain stem areas: the nucleus tractus solitarius (NTS) (Holstege et al. 1985;Gray and Magnuson 1987), caudal ventrolateral medulla (CVLM) (Giancola et al. 1993), and dorsal nucleus of the vagus (DMV) (Gray and Magnuson 1987;Hopkins 1987), supporting the role of the BNST in the regulation of autonomic responses.Its rich connections with the amygdala and PVN sug-

Anxiogenic and aversive effects of corticotropin-releasing factor (CRF) in the bed nucleus of the stria terminalis in the rat: role of CRF receptor subtypes

“…These observations are consistent with those of other reports showing increases in stress-like behaviors following intra-BNST infusions of CRF (Ciccocioppo et al 2003;Lee and Davis 1997;Liang et al 2001;Nijsen et al 2001). Anxiogenic-like effects of CRF were not observed in animals with erroneously placed microinjection needles outside of the BNST in regions such as the lateral hypothalamus, thalamus and nucleus accumbens, indicating a degree of anatomical specificity for the observed effects of CRF.…”

“…For example, intra-BNST administration of CRF facilitates the acoustic startle reflex , enhances retention of an inhibitory avoidance task (Liang et al 2001), produces anorectic effects (Ciccocioppo et al 2003) and tachycardia (Nijsen et al 2001). Conversely, infusions of nonselective CRF antagonists into the BNST produce anxiolytic-like and anti-stress effects, such as attenuated defensive burying behavior (Greenwell et al 2004), reduced conditioned freezing and stressinduced cardiovascular abnormalities (Nijsen et al 2001), and reduced conditioned defensivesubmissive behavior in response to social defeat (Jasnow et al 2004).…”

“…For example, intra-BNST administration of CRF facilitates the acoustic startle reflex , enhances retention of an inhibitory avoidance task (Liang et al 2001), produces anorectic effects (Ciccocioppo et al 2003) and tachycardia (Nijsen et al 2001). Conversely, infusions of nonselective CRF antagonists into the BNST produce anxiolytic-like and anti-stress effects, such as attenuated defensive burying behavior (Greenwell et al 2004), reduced conditioned freezing and stressinduced cardiovascular abnormalities (Nijsen et al 2001), and reduced conditioned defensivesubmissive behavior in response to social defeat (Jasnow et al 2004). However, the BNST contains both CRF 1 and CRF 2 receptor subtypes (Chalmers et al 1995;Chen et al 2000;Rominger et al 1998;Rybnikova et al 2003;Van Pett et al 2000), and although CRF has a higher affinity for CRF 1 over CRF 2 receptors (Vaughan et al 1995), it currently unclear which of these two receptors mediates the behavioral effects of CRF in the BNST.…”

Micro-Positron Emission Tomography Imaging of Rat Brain Metabolism during Expression of Contextual Conditioning

“…It has been demonstrated that BST lesions disrupt contextual freezing in a previously shocked context (Onaka and Yagi, 1998;Nijsen et al, 2001;Sullivan et al, 2004;Resstel et al, 2008;Zimmerman and Maren, 2011), but not freezing to a conditioned cue nor fear-potentiated startle following cued fear conditioning (LeDoux et al, 1988;Walker et al, 2003). Very recently, we found that posttraining BST lesions completely disrupted the expression of contextual anxiety, as measured simultaneously with startle amplitude and freezing, in rats after reintroduction in a previously shocked context (Luyten et al, 2011c).…”

CRH: The link between hormonal-, metabolic- and behavioral responses to stress

“…or directly into the BNST resulted in tachycardiac response, which was prevented either by β-adrenergic blockers or by CRH1R antagonists (Nijsen et al 2000). On the other hand, CRH, released in the medial BNST during conditioned fear stress, contributes to cardiac stress responses, particularly by activating vagal outflow (Nijsen et al 2001).…”