Figure 6

A pharmacokinetic/pharmacodynamic (PK/PD) interaction model. To summarize these results, a model was generated of the effects of irreversible antagonism and supersensitivity on self-administration behavior of the same cocaine unit dose, and assuming that the first-order elimination rate constant of cocaine was unaltered by the treatments. Compared to baseline (green line), supersensitivity of receptors (blue line) results in a decreased satiety threshold. At the lower concentrations, the rate of elimination of cocaine is lower, as dictated by first-order kinetics, and it takes longer for the concentration to decline back to the satiety threshold, resulting in a longer inter-injection interval. Receptor antagonism by both reversible and irreversible antagonists (magenta line) results in an increased satiety threshold. At the higher concentrations, the rate of elimination of cocaine is faster and it takes a shorter time for the concentration to decline back to the elevated satiety threshold resulting on a shorter inter-injection interval. The horizontal lines represent the satiety threshold under each condition. The arrows represent the inter-injection interval duration for each condition.