Effects of low dose naloxone on morphine-induced tolerance and dependence in rats

Objective: To investigate the effects of low dose naloxone on morphine-induced tolerance and dependence in rats. Methods: Eighteen adult male Sprague-Dawley rats were randomly assigned into group M,group MN1,and group MN2（n=6）. Rats in group M received 6mg/kg of morphine. Rats in groups MN1 and MN2 were given different doses of naloxone（100ng/kg,10ng/kg）with 6mg/kg of morphine.Pain threshold was determined at thirty minutes after subcutaneous injection of morphine or mixture of morphine and naloxone.Training of conditioned place preference（CPP）was carried out from day one to day eight,and CPP was tested after the last 24h training. Results: The stay time in a morphine-paired white compartment was significantly prolonged. Compared with group M,CPP scores for groups MN1 and MN2 were significantly decreased（P＜0.01）. Compared with the first three days,the pain threshold in group M was significantly decreased up to the last day（P＜0.01）,and the descending pain threshold level in group M was higher than that in groups MN1 and MN2. Conclusion: The dose of naloxone,ranging 10-100ng/kg,can restrain the formation of tolerance and dependence induced by chronic morphine administration.