Unpredictability as a modulator of drug self-administration: Relevance for substance-use disorders

Drug self-administration has been regarded as a gold-standard preclinical model of addiction and substance-use disorder (SUD). However, investigators are becoming increasingly aware, that certain aspects of addiction or SUDs experienced by humans are not accurately captured in our preclinical self-administration models. The current review will focus on two such aspects of current preclinical drug self-administration models: 1) Predictable vs. unpredictable drug access in terms of the time and effort put into obtaining drugs (i.e., response requirement) and drug quality (i.e., amount) and 2) rich vs. lean access to drugs. Some behavioral and neurobiological mechanisms that could contribute to excessive allocation of behavior toward drug-seeking and drug-taking at the expense of engaging in nondrug-related activities are discussed, and some directions for future research are identified. Based on the experiments reviewed, lean and unpredictable drug access could worsen drug-seeking and drug-taking behavior in individuals with SUDs. Once more fully explored, this area of research will help determine whether and how unpredictable and lean cost requirements affect drug self-administration in preclinical laboratory studies with nonhuman subjects and will help determine whether incorporating these conditions in current self-administration models will increase their predictive validity.