EFFECTS OF NALTREXONE PELLET IMPLANTATION ON MORPHINE-TOLERANCE AND PHYSICAL-DEPENDENCE IN THE RAT

1. The effect of naltrexone pellets containing either 10 or 30 mg of n altrexone base on the development of tolerance and physical dependence on morphine was assessed in male Sprague-Dawley rats. Tolerance-depen dence on morphine was induced by s.c. implantation of six morphine pel lets, each containing 75 mg morphine base for 7 days. 2. Naltrexone pe llet implantation blocked the development of tolerance to the analgesi c and hyperthermic effects of morphine. Similarly, naltrexone pellet i mplantation reversed morphine withdrawal-induced body weight loss. The effect of pellets containing 10 and 30 mg naltrexone did not differ. 3. The effect of naltrexone (10 mg) pellet implantation on various sig ns of naltrexone-precipitated withdrawal such as body weight loss, hyp othermia and increases in urinary and fecal output was investigated. N altrexone pellet implantation did not alter the naltrexone-precipitate d withdrawal-induced body weight loss. Concurrent naltrexone pellet im plantation blocked the naltrexone-precipitated withdrawal-induced hypo thermia, increased fecal and urinary output in morphine-dependent rats . 4. These results indicate that a single pellet of 10 mg of naltrexon e can effectively block morphine tolerance and physical dependence in the rat. Such a procedure may be useful in studying biochemical, endoc rinological and immunological mechanisms involved in opioid addiction processes.