Central nervous system and gut interactions: dopamine and experimental gastroduodenal lesions

There is increasing evidence for brain regulation of gastroduodenal function and pathological responses. This laboratory has demonstrated a significant role for dopamine (DA) as a modulator of gastrointestinal function and disease. Using models of both acute (ethanol restraint stress; cysteamine) and chronic (iodoacetamide-induced gastritis) gastroduodenal mucosal injury, as well as tests of gastric secretory function (conscious basal gastric acid secretion; pylorus ligation; ex vivo gastric chamber), we have shown that DA, particularly DA1/D1 receptor agonists are powerful gastroprotective agents. This action is demonstrable upon peripheral administration as well as central (particularly intramesolimbic) administration. DA1/D1 agonists such as SKF38393 and SKF75670C reduce experimental gastric mucosal injury and secretion while antagonists of these receptors, including SCH23390, worsen experimental gastroduodenal lesions and augment secretion. That there exists a significant central component to DA-induced gastroprotection is demonstrated by data showing that rats assessed as anxiety prone, develop a greater degree of experimentally induced gastric damage, require greater amounts of DA agonists for 50% gastroprotection and respond to exogenous stress challenge with greater central DA turnover and loss, relative to rats assessed as low in anxiety. Very recently, we showed that dopamine D4 receptor blockade by clozapine and activation of dopamine D3 receptors by 7-hydroxy-N, N-di-n-propyl-2-aminotetralin (7-OHDPAT) are also associated with antiscretory and gastroprotective effects.(ABSTRACT TRUNCATED AT 250 WORDS)