Stress, the brain, and the gastric mucosa

Exposure of rats to 2 hours of cold water restraint is associated with both macroscopic and microscopic gastric mucosal injury. Administration of neurotensin into the lateral ventricle or into the nucleus accumbens, one of the mesolimbic dopamine system nuclei, is associated with protection when given before exposure to cold water restraint. Under conditions of cold water restraint, pretreatment with central neurotensin is associated with maintenance of gastric mucosal blood flow and an increase in endogenous gastric mucosal PGE2 activity. In addition, pretreatment with 6-hydroxy dopamine into the mesolimbic nuclei, which depletes them of endogenous dopamine, prior to exposure to cold water restraint, ameliorates the protective effect of central neurotensin. Centrally administered neurotensin inhibits basal, pentagastrin-, carbachol-, and 2-deoxy-D-glucose-induced but not histamine-induced gastric acid secretion. This antisecretory effect is ameliorated by parenteral pretreatment with haloperidol and domperidone. Taken together, these observations support the hypothesis that centrally administered neurotensin, particularly into the nuclei of the mesolimbic dopamine system, confers protection against gastric mucosal injury produced by 2 hours of cold water restraint. This affect may be due, in part, to inhibition of acid secretion and maintenance of mucosal blood flow mediated by an increase in gastric mucosal PGE2 activity.