Prolonged tolerance, dependence and abstinence following subcutaneous morphine pellet implantation in the rat☆

摘要: Abstract Opiate withdrawal is a common occurrence in human opiate addicts that not life threatening but hypothesized to be significant factor which may contribute drug taking behavior these dependent individuals. The purpose of this study was compare the time course for development tolerance, dependence and abstinence using rat model. Rats were made by implantation 2 morphine pellets s.c. (75 mg base). Morphine implanted rats exhibited analgesia as measured tail-dip assay, up 12 h post-implant after tolerance resulted tail-flick latencies returning level control rats. Withdrawal evaluated injection antagonist, naloxone (1 mg/kg s.c.). Rating syndrome revealed signs 3 became increasingly intense 24 post-implant. could precipitated at least 13 days post-implant, while 18 almost no observed. Plasma levels following remained relatively stable from 3–12 post-implantation. These results further extend characterization subcutaneous pellet implantation. also suggest develops within first follows tolerance. evolution physical under similar experimental conditions critical design future studies examine neural bases phenomena.