Naloxone modulates body and organ growth of rats: Dependency on the duration of opioid receptor blockade and stereospecificity

Endogenous opioid systems (i.e., endogenous opioids and opioid receptors) act in the trophic regulation of biological development. Opioid antagonist paradigms have served to elucidate the nature of this relationship. If growth is mediated at the level of the opioid receptor, one would expect that this interaction would be stereospecific. This study shows that daily injections of 20-60 mg/kg (-) naloxone, given chronically throughout the preweaning period, depress body weight when monitored at Day 21. Opioid challenge experiments using nociceptive measures show that these dosages of (-) naloxone invoked an opioid receptor blockade for no more than 10-12 hr/day. A dosage of 100 mg/kg (-) naloxone, which blocked the opioid receptor for 12-16 hr/day, did not alter body weight in comparison to control levels. In subsequent experiments, 40 mg/kg (-) naloxone depressed body weight of 21-day-old rats, and the wet weights of the liver, spleen, thymus, heart, and triceps surae muscle from these animals were subnormal. A dosage of 40 mg/kg (+) naloxone did not alter growth. These results show that opioid action in regard to growth is stereospecific and dependent on the duration of opioid receptor blockade, providing additional evidence that endogenous opioid systems play an important role in developmental events.