Acquisition Operant conditioning represents the behavioral paradigm underlying<unk>  studies. Although not always required, subjects may be first pre-trained to perform some action, such as a lever press or nose poke to receive a food or water reward (under food- or water- restricted conditions, respectively). Following this initial training, the reinforcer is replaced by a test drug to be administered by one of the following methods: oral, inhalation, intracerebral, intravenous. Intravenous catheterization is used most commonly because it maximizes bioavailability and has a rapid onset, although is inappropriate for drugs taken orally, such as alcohol. Humans suffering from addiction often resort to intravenous drug use for similar reasons, so this route of<unk>  increases the face validity of the construct. Maintenance Upon presentation of the drug to the subject, a number of experimental variables might be manipulated to test hypotheses: Dose-response relationship Dose-response relationship in cocaine self-administering mice. Both humans and animals will adjust the rate and number of drug infusions to maintain stable rewarding blood levels of drugs, like cocaine. A dilute dose of cocaine will be administered intravenously at a faster rate than a concentrated dose of cocaine. Reinforcement schedules Continuous reinforcement: A single operant response triggers the dispense of a single dose of the reinforcer. A time-out period may follow each operant response that successfully yields a dose of reinforcer; during this period the lever used in training may be retracted preventing the animal from making further responses. Alternatively, operant responses will fail to produce drug<unk>  allowing previous injections to take effect. Moreover, time-outs also help prevent subjects from overdosing during<unk>  experiments. Fixed-ratio studies require a predefined number of operant responses to dispense one unit of the reinforcer. Standard fixed ratio reinforcement schedules include FR5 and FR10, requiring 5 and 10 operant responses to dispense a unit of reinforcer, respectively. Progressive ratio reinforcement schedules utilize a multiplicative increase in the number of operant responses required to dispense a unit of the reinforcer. For example, successive trials might require 5 operant responses per unit of reward, then 10 responses per unit of reward, then 15, and so on. The number of operant responses required per unit of reinforcer may be altered after each trial, each session, or any other time period as defined by the experimenter. Progressive ratio reinforcement schedules provide information about the extent that a pharmacological agent is reinforcing through the breakpoint. The breakpoint is the number of operant responses at which the subject ceases engaging in<unk> , defined by some period of time between operant responses (generally up to an hour). Fixed interval (FI) schedules require that a set amount of time pass 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<unk> line 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<unk>  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 limited to) acute stressors such as foot-shock or social defeat stress. In many cases, it appears that social stress can potentiate drug reinstatement just as strongly as exposure to the drug itself
Self-administration
Self-care
Clean living movement
Harm avoidance
Perspiration
Heal 
Out-of-body experience
Dosing