Naltrexone modulates body and brain development in rats: a role for endogenous opioid systems in growth.
Preweaning rats receiving daily injections of 20, 50, or 100 mg/kg naltrexone, a potent opiate antagonist, had body and brain weights that were increased 16-22% and 6-13%, respectively, from control levels on day 21 (weaning). All of these dosages of naltrexone blocked the opiate receptor for 24 hr/day as measured in opiate challenge experiments. Dosages of 0.1, 1, and 10 mg/kg naltrexone, which blocked the opiate receptor for less than 12 hr/day, inhibited growth. Repetitive administration of low dosages (3 mg/kg naltrexone, 3 times daily), which blocked the receptor 24 hr/day, increased body and brain development by 31% and 10%, respectively, whereas a cumulative dosage of 9 mg/kg naltrexone given once daily retarded growth. These results show that developmental events are dictated by the duration of opiate receptor blockade and provide compelling evidence that endogenous opioid systems play a crucial role in growth.
D000375:Aging; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000254:growth & development*; D005260:Female; D008297:Male; D009270:Naloxone / Q000031:analogs & derivatives*; D009271:Naltrexone / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology
D011957:Receptors, Opioid; D009270:Naloxone; D009271:Naltrexone