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Neuroscience. 2013;255:278-91. doi: 10.1016/j.neuroscience.2013.09.032. Epub 2013 Sep 23.

Effects of hypocretin and norepinephrine interaction in bed nucleus of the stria terminalis on arterial pressure.

Author information

1
Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON N6A 5C1, Canada. Electronic address: john.ciriello@schulich.uwo.ca.

Abstract

Forebrain neuronal circuits containing hypocretin-1 (hcrt-1) and norepinephrine (NE) are important components of central arousal-related processes. Recently, these two systems have been shown to have an overlapping distribution within the bed nucleus of the stria terminalis (BST), a limbic structure activated by stressful challenges, and which functions to adjust arterial pressure (AP) and heart rate (HR) to the stressor. However, whether hcrt-1 and NE interact in BST to alter cardiovascular function is unknown. Experiments were done in urethane-α-chloralose anesthetized, paralyzed, and artificially ventilated male Wistar rats to investigate the effect of hcrt-1 and NE on the cardiovascular responses elicited by l-glutamate (Glu) stimulation of BST neurons. Microinjections of hcrt-1, NE or tyramine into BST attenuated the decrease in AP and HR to Glu stimulation of BST. Additionally, combined injections of hcrt-1 with NE or tyramine did not elicit a greater attenuation than either compound alone. Furthermore, injections into BST of the α2-adrenergic receptor (α2-AR) antagonist yohimbine, but not the α1-AR antagonist 2-{[β-(4-hydroxyphenyl)ethyl]aminomethyl}-1-tetralone hydrochloride, blocked both the hcrt-1 and NE-induced inhibition of the BST cardiovascular depressors responses. Finally, injections into BST of the GABAA receptor antagonist bicuculline, but not the GABAB receptor antagonist phaclofen, blocked the hcrt-1 and NE attenuation of the BST Glu-induced depressor and bradycardia responses. These data suggest that hcrt-1 effects in BST are mediated by NE neurons, and hcrt-1 likely acts to facilitate the synaptic release of NE. NE neurons, acting through α2-AR may activate Gabaergic neurons in BST, which in turn through the activation of GABAA receptors inhibit a BST sympathoinhibitory pathway. Taken together, these data suggest that hcrt-1 pathways to BST through their interaction with NE and Gabaergic neurons may function in the coordination of cardiovascular responses associated with different behavioral states.

KEYWORDS:

2-{[β-(4-hydroxyphenyl)ethyl]aminome thyl}-1-tetralone hydrochloride; 3rd ventricle; A1/A2/A5; AMB; AMG; AP; AR; BIC; BST; CVLM; GABA; GABA(A)-receptor antagonist bicuculline methiodide; Glu; HEAT hydrochloride; HR; IML; LH; LPO; LS; MAP; MPN; MS; NE; RVLM; SF; SI; SNS; V3; VL; VN; ac; adrenergic receptor; adrenergic receptors; amygdala; anterior commissure; arterial pressure; bed nucleus of the stria terminalis; brainstem noradrenergic/norepinephrine cell groups; cardiovascular regulation; caudal ventrolateral medulla; cc; corpus callosum; extended amygdala; fornix; fx; hcrt-1; heart rate; hypocretin-1; int; intermediolateral cell column; internal capsule; l-glutamate; lateral hypothalamus; lateral preoptic area; lateral septum; lateral ventricle; mean arterial pressure; medial preoptic nucleus; medial septum; norepinephrine/noradrenaline; nucleus ambiguus; oc; optic chiasma; orexin; rostral ventrolateral medulla; septofimbrial nucleus; st; stress; stria terminalis; substantia innominata; sympathetic nervous system; vagus nerve

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