Opioid antagonist-induced regulation of organ development

Abstract

Naltrexone, a potent opioid antagonist, was given to preweaning rats in order to explore the influence of endogenous opioid systems on organogenesis. Sprague-Dawley rats were injected (SC) daily with either 1 or 50 mg/kg naltrexone to invoke a temporary or complete blockade, respectively, of opioid receptors; animals injected with sterile water served as controls. At weaning (Day 21), wet and dry weights, relative organ weight, and tissue water content were determined in 10 organ systems. Naltrexone's effects on growth depended on dosage, sex, and the organ system examined. In general, dosages of 1 and 50 mg/kg naltrexone caused significant decreases and increases, respectively, in organ weight. These changes in wet weight were not due to the state of hydration, but rather to dry weight, indicating that the content of cellular matter was altered. The changes in wet weight were similar to those for body weight, suggesting that a proportional increase or decrease in animal growth took place. Although the same organs in males and females within a dosage group were influenced by naltrexone, and usually to a similar degree, a dosage of 1 mg/kg naltrexone often affected different organ systems than the 50 mg/kg dosage. These results serve as the foundation for subsequent investigations directed towards delineating the role of endogenous opioid systems in developmental biology.