Quantitative analysis of concentration-response curves for precipitated abstinence responses in the opiate-dependent...

Our group has introduced a theoretical model of drug-receptor-effector interactions that can account for most of the kinetic aspects of opiate dependence and abstinence. The present study analyzes the experimental concentration-response curves for precipitated abstinence responses in the isolated guinea pig ileum and compares them with the curves generated by the mathematical model. Two experimental series were included: in the first, the effects of morphine exposure time on dependence development were analyzed; in the second, the effects of morphine concentration were studied. The results show that both the exposure time and morphine concentration determine the magnitude of precipitated abstinence responses. Dependence can be detected after exposure times to opiates as short as 7.5 min. The concentration-response curves for abstinence responses precipitated by naloxone in ilea exposed to morphine for different periods showed: 1) an initial increase in Emax; 2) a parallel shift to the left in the position of the abstinence curves as dependence develops; and 3) an asymptotic limit to the displacement on the left. The results presented here fit well with theoretical predictions. Practical and theoretical implications are discussed.