U-shaped dose response in behavioral pharmacology: Historical foundations

This article assesses the historical foundations of U-shaped dose-responses in behavioral pharmacology and toxicology with particular emphasis on schedules of reinforcement. Quantitative features of the drug dose response, which are consistent with the hormetic dose response model, are detailed along with possible mechanistic foundations to account for low-dose stimulation and high-dose inhibition responses. The article provides a reinterpretation of the biphasic dose response in the fixed interval (FI) schedule of reinforcement.