Administration of opiate receptor antagonist inhibits mucosal atrophy of the gut in fasting rats

Objective. The objective of this study was to determine whether the opiate mu receptor antagonist naloxone mould prevent atrophy of the gut in 24-h-fa sted rats. Methods. Male Sprague-Dawley rats (n = 76, body weight 200-225 g) were cath eterized in the jugular vein on Day 0. The rats were fed standard rat chow for 4 days. On Day 4, the diet was changed to the standard liquid diet, and the rats were allowed free access to the liquid diet. On Day 7, the rats w ere randomized into five groups: (1) free fed, (2) free fed plus naloxone, (3) pair fed, (4) fasting, (5) free fed plus morphine, (6) fasting plus nal oxone, Either naloxone (0.16 mg/kg/h) or morphine (0.21 mg/kg/h) was contin uously infused via venous catheter for 24 h. On Day 8, 24 h after fasting o r free feeding; the animals were sacrificed. Results. Twenty-four hours of fasting caused atrophy of the jejanum and ele vated morphine levels in the brain (free fed, 931.3 +/- 122.3 fmol/g, vs fa sting 1419.0 +/- 150.0, P < 0.05). Morphine infusion reduced villus height, mucosal weight, and protein content in jejunum as compared with the free f ed rats receiving saline. Administration of naloxone caused an increase in villus height (fasting, 587.0 +/- 25.8 mu m, vs fasting plus naloxone, 670. 0 +/- 17.4, P < 0.05), mucosal weight (fasting, 17.4 +/- 1.8 mg/cm, vs fast ing plus naloxone, 22.6 +/- 1.9, P < 0,05), and protein content (fasting, 1 3.5 +/- 0.7 mu g/cm, vs fasting plus naloxone, 16.7 +/- 0.6, P < 0.05) in j ejunum. Conclusion. Mucosal atrophy of the jejunum is caused by endogenous opioid i n fasting rats. (C) 2000 Academic Press.