Vagally mediated gastric effects of brain stem α₂-adrenoceptor activation in stressed rats

Abstract

Chronic stress exerts vagally dependent effects to disrupt gastric motility; previous studies have shown that, among other nuclei, A2 neurons are involved in mediating these effects. Several studies have also shown robust in vitro and in vivo effects of α2-adrenoceptor agonists on vagal motoneurons. We have demonstrated previously that brainstem vagal neurocircuits undergo remodeling following acute stress; however, the effects following brief periods of chronic stress have not been investigated. Our aim, therefore, was to test the hypothesis that different types of chronic stress influence gastric tone and motility by inducing plasticity in the response of vagal neurocircuits to α-adrenoreceptor agonists. In rats that underwent 5 days of either homotypic or heterotypic stress loading, we applied the α-adrenoceptor agonist, UK14304, either by in vitro brainstem perfusion to examine its ability to modulate GABAergic synaptic inputs to vagal motoneurons or in vivo brainstem microinjection to observe actions to modulate antral tone and motility. In neurons from naïve rats, GABAergic currents were unresponsive to exogenous application of UK14304. In contrast, GABAergic currents were inhibited by UK14304 in all neurons from homotypic and, in a subpopulation of neurons, heterotypic stressed rats. In control rats, UK14304 microinjection inhibited gastric tone and motility via withdrawal of vagal cholinergic tone; in heterotypic stressed rats, the larger inhibition of antrum tone was due to a concomitant activation of peripheral nonadrenergic, noncholinergic pathways. These data suggest that stress induces plasticity in brainstem vagal neurocircuits, leading to an upregulation of α-mediated responses. NEW & NOTEWORTHY Catecholaminergic neurons of the A2 area play a relevant role in stress-related dysfunction of the gastric antrum. Brief periods of chronic stress load induce plastic changes in the actions of adrenoceptors on vagal brainstem neurocircuits.

Hypothalamic–vagal oxytocinergic neurocircuitry modulates gastric emptying and motility following stress

“…2011; Jiang et al . 2018 a , b ). This adaptive response of GI motility following CHo is associated with an increase in OXT expression in PVN (Zheng et al .…”

Advances in the physiology of gastric emptying

“…Moreover, within the NTS, the GABA, non‐GABA, and GLUT neurons are interconnected . NTS‐CC‐e neurons may also act to inhibit DMV‐C‐e neurons via the α2‐receptors . Thus, NTS neurons exert a precise inhibitory regulation of the GEVC.…”

“…74 NTS-CC-e neurons may also act to inhibit DMV-C-e neurons via the α2-receptors. 62,75 Thus, NTS neurons exert a precise inhibitory regulation of the GEVC. DMV-C-e neurons also receive GABAergic inhibitory input from area postrema.…”

Role of estrogen and stress on the brain-gut axis

“…Rats that underwent chronic variable stress showed a larger inhibition of antrum tone in response to ␣2-adreneceptor activation compared with control or rats that underwent chronic repetitive stress. The translocation of ␣2adreneceptor on GABAergic terminal of NTS-DMV synapses, combined with changes in intrinsic DMV neuronal excitability, may be responsible for the maladaptive response to ␣2-adreneceptor activation on gastric tone and motility (49). More detailed investigations on the mechanisms of neuroplasticity of vagal neurocircuits that occurred following chronic stress, as well as how these changes contribute to the adaptive or maladaptive response to stress, are certainly needed.…”