Effects of Catecholamines on Gastric Functions in Stressed Rats
Authors: Jiang Yanyan , Browning Kirsteen N , Toti Luca , Travagli R. Alberto 
Published: November 2023

Stress maladaptation plays a critical role in the development and exacerbation of functional gastrointestinal (GI) disorders. We have shown recently that stress induces plasticity in the oxytocin modulation of brainstem vagal neurocircuits controlling GI functions (Browning et al. 2014). Similarly, anatomical and neurochemical data suggest that stress alters the levels of catecholamines in the brainstem A2 area, which comprises vagal neurocircuits.

The aim of this study was to test the hypothesis that stress alters the response of vagal motoneurons to catecholamines.

Male SD rats were subdivided in the following groups: i) control; ii) chronic repetitive homotypic (restraint) stress, rats in this group show adaptation to stress; iii) chronic repetitive heterotypic (restraint, forced swim, water avoidance and cold) stress, rats in this group do not show adaptation to stress.

Subsequently, miniature strain gauges were sutured onto the anterior gastric wall of anesthetized rats to monitor corpus and antrum tone and motility. After exposure of the dorsal brainstem a micropipette was inserted in the DMV to microinject the indirect sympathomimetic tyramine (4.5nmoles/60nl). In control and homotypic stressed rats, microinjection of tyramine decreased corpus tone (−140±13 and −130±15mg, N=21 and 19, respectively) and suppressed gastric motility (58±8% and 50±8% of baseline, respectively). Conversely, in the heterotypic stressed rats group, tyramine decreased corpus tone by −93±14mg and motility to 47±7% of baseline (N=14, p<0.05 vs control and homotypic stressed rats). In all groups the response to tyramine was attenuated significantly by the α2 adrenoceptor antagonist yohimbine. These data suggest that catecholamines decrease gastric tone and motility, and the response is altered in heterotypic stress rats.

In vitro whole cell patch clamp recordings of GABAergic inhibitory postsynaptic currents (IPSCs) were done in identified gastric‐projecting DMV neurons. In control animals, perfusion of the a2‐receptor agonist UK14304 has no effect on amplitude of evoked IPSC (N=10) or on frequency of miniature IPSC (N=9). When brainstem cAMP levels were elevated with forskolin or CRF, however, UK14304 decreased eIPSC amplitude to 76±7% of the baseline in 3 of 3 DMV neurons, or decreased mIPSC frequency to 67±5% of baseline in 6 of 6 neurons tested, respectively. In contrast, in homotypic stressed rats perfusion with UK14304 decreased the amplitude of eIPSC in 12 of 17 neurons (77±1% of baseline) and mIPSC frequency in 7 of 7 neurons (40±8% of baseline, p<0.05). In heterotypic rats, UK14304 decreased the eIPSC amplitude in 4 of 12 neurons (50±11% of baseline) and mIPSC frequency in 4 of 13 neurons (58±9% of baseline).

Taken together, our data suggest the vagal neurocircuits response to catecholamines is modulated by stress exposure, and stress adaptation, as in homotypic stressed rats, may be determined by a plastic response of GABAergic circuit to catecholamines.

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NIH DK 55530