CENTRAL AND PERIPHERAL INVOLVEMENT OF ENDOGENOUS OPIOID-PEPTIDES IN GASTRIC PROTECTION IN STRESSED RATS

The effects of intraperitoneal and intracerebroventricular administrat ion of the inhibitor of endopeptidase EC 24.11 (enkephalinase), thiorp han, and the synthetic enkephalin analogue [D-Ala(2)-Met(5)]enkephalin amide (DALA) were investigated in cold-restraint-stressed rats. Drugs were administered alone or after pretreatment with naloxone or naloxon e methiodide given 20 min prior to the drugs, Thiorphan and DALA, admi nistered centrally (4 mu g i.c.v./rat) or peripherally (400 mu g/kg), induced a significant gastric protection, Prior treatment with naloxon e s.c. (1 mg/kg) inhibited the effect induced by i.c.v. or i.p. inject ions of thiorphan or DALA, In contrast, s.c. administration of naloxon e methiodide (1 mg/kg) did not affect the response induced by central administration of thiorphan or DALA, but was able to prevent that of t hiorphan or DALA when they were administered i.p. These data strongly support the hypothesis of a central and peripheral involvement of endo genous opioid peptides in gastric protection in stressed rats.