Bidirectional Brain-gut Interactions: Involvement of Noradrenergic Transmission Within the Ventral Part of the Bed Nucleus of the Stria Terminalis

Introduction: Although the important roles of bidirectional interactions between the brain and gut in stress and emotional responses have long been recognized, the underlying neuronal mechanisms remain unclear. The bed nucleus of the stria terminalis (BNST) is a limbic structure involved in stress responses and negative affective states, such as anxiety and depression. We have previously demonstrated that noradrenergic transmission within the ventral part of the BNST (vBNST) plays a crucial role in anxiety-like behaviors and pain-induced aversion.

Objectives: This study aimed to examine the involvement of noradrenergic transmission via β-adrenoceptors within the vBNST in bidirectional brain-gut interactions.

Methods: We measured the gastric distention (GD)-induced noradrenaline release within the vBNST of freely moving rats using an in vivo microdialysis technique. Gastric emptying and intestinal transit were examined following intra-vBNST injections of isoproterenol, a β-adrenoceptor agonist, in the absence or presence of the coadministration of timolol, a β-adrenoceptor antagonist.

Results: Gastric distention at a higher pressure (45 mm Hg) but not at a lower pressure (25 mm Hg) resulted in a significant increase in extracellular noradrenaline levels within the vBNST. Intra-vBNST injections of isoproterenol (30 nmol/side) induced significant reductions in gastric emptying and small intestinal transit, both of which were reversed by the coadministration of timolol (30 nmol/side).

Conclusion: Noradrenergic transmission via β-adrenoceptors within the vBNST was involved in bidirectional brain-gut interactions. These findings suggest that gastric dysfunction may induce negative affective states via the enhanced release of noradrenaline within the vBNST which, in turn, may cause gastrointestinal impairments.