Roles of noradrenergic transmission within the ventral part of the bed nucleus of the stria terminalis in bidirectional brain-intestine interactions

Abstract

Aims: The bed nucleus of the stria terminalis (BNST) is a limbic structure mediating autonomic and neuroendocrine responses and negative affective states such as anxiety and fear. We previously demonstrated that noradrenergic transmission via β-adrenoceptors within the ventral part of BNST (vBNST) is involved in bidirectional interactions between the brain and the upper gastrointestinal (GI) tract. The present study aimed to examine the roles of intra-vBNST noradrenergic transmission via β-adrenoceptors in bidirectional interactions between the brain and lower GI tract. Methods: In vivo microdialysis experiments were performed to examine colorectal distention (CRD)-induced noradrenaline release within the vBNST of freely moving male Sprague-Dawley rats. Colonic transit and abdominal pain perception were examined following intra-vBNST injections of isoproterenol, a β-adrenoceptor agonist, with and without co-administration of timolol, a β-adrenoceptor antagonist. Results: CRD increased extracellular noradrenaline levels within the vBNST and evoked abdominal contractions in a pressure-dependent manner (30-60 mm Hg). Bilateral intra-vBNST injections of isoproterenol (30 nmol/side) significantly increased CRD (30 mm Hg)-induced abdominal contractions. Intra-vBNST injections of isoproterenol (30 nmol/side) significantly increased colonic transit, which was reversed by co-administration of timolol (30 nmol/side). Conclusion: The results of this study suggest (a) the existence of a positive feedback loop between intra-vBNST noradrenaline release and abdominal pain perception, and (b) the modulation of colonic motility by intra-vBNST noradrenergic transmission via β-adrenoceptors. Dysfunction of the lower GI tract may increase noradrenaline release within the vBNST, which, in turn, may exacerbate impairment of its motility and pain perception.