Assistant ProfessorDepartment of Psychiatry and Human BehaviorOffice: G129(601) 815-5619Email
Converging evidence has established that manipulating variables such as the cost (i.e., number of responses) required to earn drug reinforcers, or the dose of drug available per delivery, can reduce drug choice and more generally, drug self-administration. The effects of these manipulations on drug choice and drug self-administration have been studied primarily with predictable, often low-cost schedules of delivery, and this may impede generalization from preclinical models to the natural environment. The choice to take a drug when drug and competing nondrug options are available under qualitatively different schedules of availability represents a more translational approach to what individuals with substance-use disorders (SUDs) often experience. For example, predictable amounts of work (i.e., most jobs) result in predictable availability of a paycheck, whereas illicit drugs are relatively unpredictable in terms of their quality, location, price, and time and effort to obtain.
Unpredictable (i.e., variable-ratio) schedules of reinforcement result in clear behavioral differences relative to predictable (i.e., fixed-ratio) schedules. For example, behavior maintained by unpredictable schedules of nondrug delivery occurs at a high rate, with short pauses between response bouts, and is more resistant to extinction. We recently found that rhesus monkeys choose variable cocaine over fixed cocaine delivery, extending work with nondrug outcomes to a drug of abuse. While many factors contribute to SUDs, the primary premise of my research program is that unpredictable drug access may be a common feature of the environment that plays a key role in perseverative drug taking.
Under the basic choice arrangement, male and female rhesus monkeys choose between cocaine and food under fixed and variable schedules that require, on average, an equal number of responses. Early studies using this choice arrangement indicate that unpredictable availability could contribute to excessive allocation of behavior toward procuring drugs at the expense of more predictable, nondrug alternatives. Conversely, if unpredictable food delivery decreases cocaine choice, it would support the use of novel, easily implemented modifications to therapies like contingency management or treatments that incorporate nondrug reinforcers as a treatment component.
Another interest of mine is whether subjects with a long history of unpredictable drug access will work harder for that drug (i.e., under a progressive-ratio schedule) following their unpredictable exposure period relative to more predictable drug-access conditions. This research is in the early stages but if confirmed, would implicate unpredictable access as a key factor to perseverative drug-seeking behavior seen in individuals with SUDs. This will eventually allow us to evaluate whether placing drugs under predictable schedules can reduce the deleterious effects of a history of unpredictable access, providing a behavioral mechanism for the success of agonist replacement therapies which provide a condition of predictable drug access. Conversely, we will be able to evaluate the extent to which placing a drug with a history of predictable access under unpredictable-access conditions exacerbates drug-seeking behavior, supporting predictability as a behavioral mechanism for the potential deleterious effects of defunding agonist replacement therapy or discontinuation of prescription drugs that can result in a transition to unpredictable, illicit-substance use.