Toward a mathematical description of dose-effect functions for self-administered drugs in laboratory animal models

Rationale: The interpretation of dose-effect functions for self-administered drugs remains elusive. Since, for self-administered drugs, the amount of drug in an animal depends on its behavior, a mathematical theory of drug self-administration must include terms relevant to receptor theory, as well as a description of how an organism's behavior affects the amount of drug in the animal over time. Objective: A theory was constructed in which the ability of a dose to maintain responding was described in terms of receptor theory and the function relating rate of responding to amount of drug self-administered. The main predictions of the theory were that: 1) there should be no ascending limb for drugs self-administered under ratio schedules, 2) running rate of response should not change as a function of dose and, 3) pause duration should be an exponential function of dose. Results: Low doses of cocaine were; either self-administered at high rates, or not at all. Run rates, though somewhat variable, did not change as an orderly function of dose. Pause duration could be well described by an exponential function. Conclusions: The theory provides an acceptable, though no doubt preliminary, description of drug self-administration.