Enhanced lithogenicity of bile following chronic morphine administration to female guinea pigs

Acute and chronic opiate exposure impairs the emptying of bile from the gallbladder. In this study, the effects of a 4-day morphine regimen on bile composition were examined. Bile acids and phospholipids concentration of bile obtained from the gallbladder of female morphine-treated (MT) guinea pigs were reduced by 60% and 80% respectively, resulting in a highly lithogenic bile. Concentrations of bile acids and phospholipids of spontaneously secreted bile were not reduced. However, the lithogenicity of the hepatic bile in MT animals was still increased because of a 10 fold elevation in cholesterol concentration. Ratios of solute concentrations of stored and freshly secreted bile indicated that morphine also impaired the ability of the gallbladder to concentrate bile. Thus chronic morphine exposure increased bile lithogenicity by increasing cholesterol content and also by diluting the bile in the gallbladder. These alterations and the previously described biliary stasis indicates that chronic opiate and endogenous opioid exposure should facilitate gallstone formation.