A study of the actions of naloxone and morphine on gastric acid secretion and gastric mucosal damage in the rat.

There exists a considerable controversy in the literature with regard to the effect of either opiate receptor blockade or that of morphine in different gastric and intestinal ulcer models in the rat. We performed experiments to evaluate the effects of naloxone and morphine on gastric acid secretion and gastric mucosal damage in different experimental models of gastric mucosal injury, namely in indomethacin-, HCl (0.6N)- and ethanol (96%)-models. We found that: 1) 10 mg/kg naloxone i.p. given twice, effectively protected gastric mucosa against indomethacin (30 mg/kg i.p.) and against the acid-dependent injury caused by 0.6 N HCl (1 mL i.g.), but not against the non acid-dependent injury caused by 96% ethanol (1 mL i.g.); 2) morphine (10 + 10 mg/kg i.p.) increased ulcers in the HCl-model, but had no effect in the two other models; 3) this ulcer-aggravating effect of morphine in the HCl-model was blocked by pretreatment of 2 mg/kg i.p. naloxone; and 4) both naloxone (5 + 5 and 10 + 10 mg/kg i.p.) and morphine (10 + 10 mg/kg i.p.) significantly decreased gastric acid secretion in 1-h pylorus ligated rats. We conclude that: 1) naloxone dose-dependently protects against the indomethacin- and HCl-, but not against the ethanol-induced gastric mucosal damage; 2) morphine aggravates the HCl-induced ulcerogenesis; and 3) both opioid receptor agonist and antagonist decrease gastric acid secretion.