Opioid dependence and tolerance in the guinea-pig ileum in vitro

A rapid and simple method for the quantitative determination of opioid dependence and tolerance in the guinea pig ileum was introduced. Dependence, as indicated by a strong contraction of the ileum when challenged with naloxone, was produced by incubating ileum from native guinea pig with opioid at 37 degrees C for 1-6 h. The response of the ileum to naloxone was time-dependent and directly related to the normorphine concentration in the incubation fluid (10-1000 nmol/L) and to the challenge dose of naloxone (10-1000 nmol/L). There were lower naloxone-precipitated withdrawal responses in the guinea pig ileum incubated with pethidine, nalorphine and ohmefentanyl than with fentanyl, U50488H and morphine. Buprenorphine showed no withdrawal response. In spite of rapid development of dependence, segments of ileum incubated with normorphine at low concentration (10-300 nmol/L) showed no or slight tolerance to normorphine (3-fold). Only by incubating with high concentration of normorphine (1 mumol/L) was high tolerance detected. The results indicate that opioid dependence and tolerance do not develop in parallel.