between drug infusions, regardless of the number of times that the desired response is performed. This “refractory” period can prevent the animal from overdosing on a drug. Variable interval (VI) schedules of reinforcement are identical to FI schedules, except that the amount of time between reinforced operant responses varies, making it more difficult for the animal to predict when the drug will be delivered. Second-order reinforcement schedules build on basic reinforcement schedules by introducing a conditioned stimulus that has previously been paired with the reinforcer (such as the illumination of a light). Second-order schedules are built from two simpler schedules; completion of the first schedule results in the presentation of an abbreviated version conditioned stimulus, following completion of a fixed-interval, the drug is delivered, alongside the full-length conditioned stimulus. Second-order schedules result in a very high rate of operant responding at the presentation of the conditioned reinforcer becomes reinforcing in its own right. Benefits of this schedule include the ability to investigate the motivation to seek the drug, without the interference of the drug's own pharmacological effects, maintaining a high level of responding with relatively few drug infusions, reduced risk of self-administered overdose, and external validity to human populations where environmental context can provide a strong reinforcing effect for drug use. Extinction and reinstatement Extinction involves the discontinuation of a particular reinforcer in response to operant behavior, such as replacing a reinforcing drug infusion with a saline vehicle. When the reinforcing element of the operant paradigm is no longer present, a gradual reduction in operant responses results in the eventual cessation or “extinction” of the operant behavior. Reinstatement is the restoration of operant behavior to acquire a reinforcer, often triggered by external events/cues or exposure to the original reinforcer itself. Reinstatement can be broken into a few broad categories: Drug-induced reinstatement: exposure to a reinforcing drug after the extinction of drug-seeking operant behavior can often reinstate drug-seeking, and can even occur when the new drug of exposure is different from the original reinforcer. This is thought to be strongly linked to drug sensitization Cue-induced reinstatement: environmental cues associated with drug administration can trigger drug reinstatement by acting as conditioned stimuli, even during drug abstinence 1. Environmental surroundings, as well as drug-associated behavior or actions, can function as environmental cues. 2. Stress-induced reinstatement: in many cases, a stressor can reinstate drug-seeking in a drug-abstinent animal. This can include (but is not