Central nervous system has a profound role in regulation of gastric mucosal integrity. Different neuropeptides such as peptide YY, amylin, leptin, ghrelin, opioids (e.g. β-endorphin, deltorphin II, endomorphins), nociceptin, nocistatin, TLQP-21 and substance P were shown to protect the gastric mucosa in experimental ulcer models given centrally. Most of the neuropeptides induced gastroprotective action in pmolar dose range injected intracerebroventricularly (i.c.v.) or intracisternally (i.c.), endomorphins and β-endorphin, proved to be effective even in femtomoles. Dorsal vagal complex and vagal efferents have basic role in conveying the centrally initiated effect to the periphery. However, the potential role of sympathetic nervous system in centrally-induced mucosal protection has also been raised. Our previous results showed that the gastroprotective effect of opioid peptides was reduced significantly but not abolished by bilateral vagotomy. Now it was demonstrated that the protective effect of [D-Ala (2), D-Leu (5)]-ol-enkephalin (DAGO; 38 pmol), β-endorphin (10 pmol) and endomorphin-2 (0.1 pmol) injected i.c.v. was highly reduced after chemical sympathectomy by 6-OH dopamine (600 nmol i.c.v.). Simultaneously, the noradrenaline content of nucleus tractus solitarii (NTS) decreased from 1,881 ± 89 to 1,439 ± 154 pg/mg tissue (p < 0.05) in 6-OH dopamine-treated rats. The results indicate that the integrity of the adrenergic system besides the cholinergic one may also be necessary for the centrally induced gastroprotection. Further research is needed to reveal the role of sympathetic nervous system as well as the interactions between neuropeptides in maintaining gastric mucosal integrity and gastric mucosal defense.