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NIDA

NIDA Notes Glossary

animal model

An animal used as a proxy for humans in scientific research to elucidate basic biological and behavioral processes or disease mechanisms, or to test responses to treatments.

Animal models can be informative to the extent that the animals share with humans traits that are relevant to the condition under study. Rats and mice provide appropriate animal models for addiction because, like humans, they self-administer addictive drugs, continue to take drugs despite high costs and adverse consequences, experience drug withdrawal symptoms if they stop taking drugs abruptly, and return to drug use in response to environmental triggers, stress, or renewed exposure.

The term animal model can also refer to an experimental design that employs animals. Among those commonly used in addiction research are drug self-administration, conditioned place preference, and extinction training.

conditioned place preference

An experimental design used to evaluate a drug’s potential to produce rewarding psychoactive effects and motivate drug-seeking behavior.

Researchers repeatedly expose an animal to a drug in one chamber of a test cage, and subsequently place the animal in a foyer between that chamber and a second chamber that it has not learned to associate with the drug. If the drug produced positive subjective feelings, the animal will prefer, and spend more time in, the drug-associated chamber. The greater the fraction of time the animal spends in the drug-associated chamber, the stronger the drug’s rewarding and motivating effects are estimated to be.

drug dependence

A physiological state whereby abrupt discontinuation of a drug will result in withdrawal symptoms.

Drug dependence results from chronic exposure to an addictive drug. In research and clinical practice, the term “drug dependence” is often used diagnostically to indicate that a patient has developed tolerance to a drug, is subject to drug withdrawal from the drug, and also exhibits behavioral traits of addiction.

drug-seeking behavior

Activity directed at obtaining a drug. In animal studies, drug-seeking behaviors include pressing a lever to self-administer a drug and favoring a cage area associated with exposure to a drug (see conditioned place preference).

Drug-seeking behavior that is resumed or persists despite no longer achieving its goal (e.g., when the drug self-administration lever is inactivated) indicates vulnerability to relapse. Medications and other interventions that reduce animals’ drug-seeking behavior are considered to have promise as addiction treatments in relapse.

extinction training

An experimental design used to evaluate a drug’s potential to cause persistent drug-seeking behavior.

In the most common protocol, researchers train animals to press a lever to obtain an infusion of a drug (see self-administration), then disconnect the lever from the infusion pump. The animal gradually learns that pressing the lever no longer produces the drug reward, and reduces its lever pressing to zero or near-zero. The longer this takes, the more tenacious the drug’s influence on behavior is considered to be. An animal that has completed extinction training is considered to be in a state analogous to a drug abuser who has achieved abstinence (see also forced abstinence).

Extinction training is also often used to evaluate potential treatments for addiction: A medication or other intervention that reduces animals’ lever pressing during extinction training may lessen craving and help drug abusers establish and maintain abstinence. See also, reinstatement test.

forced abstinence

A procedure used to induce a state in an experimental animal corresponding to drug abstinence in a human.

Researchers train an animal to self-administer a drug and subsequently remove its access to both the self-administration apparatus (for example, by moving it to a cage with no lever) and the drug. Forced abstinence differs from extinction training in that animals become drug-free in an environment that they have not previously learned to associate with drugs. Some researchers maintain that forced abstinence more closely parallels the conditions in which drug abusers typically become abstinent.

progressive ratio schedule

In addiction science, an animal model used to evaluate a drug’s potential to motivate an animal to “work” to obtain it.

The protocol is similar to self-administration, except that the animal must perform a required activity, such as pressing a lever, more times to obtain each successive drug infusion. For example, with a 2x schedule, an animal that has pressed once for a first infusion must press twice for a second infusion, four times for a third infusion, and so on. The more infusions the animal obtains despite the escalating “work” requirement, the greater is the likelihood that abusers will continue to seek it despite rising costs.

reinstatement test

An animal model used to estimate a drug’s potential to produce persistent vulnerability to relapse following abstinence.

In preparation for reinstatement testing, an animal undergoes a self-administration protocol followed by either extinction training or forced abstinence. In the reinstatement test, the researchers expose the now-drug-free animal to a stimulus that corresponds to one of the three main triggers for human relapse to drugs: a low “priming dose” of the drug, a cue or environment that the animal has learned to associate with the experience of the drug, or a stressor. If the animal resumes its former self-administration activity, the drug is considered to predispose former users to relapse. The intensity with which the animal resumes the activity indicates the extent of relapse vulnerability.

Reinstatement testing is often performed to evaluate whether a potential treatment can reduce vulnerability to relapse. If the treatment is effective, animals that receive it will reinstate self-administration activity to a lesser degree than a comparison group of untreated animals.

self-administer

An experimental design used to evaluate whether a drug has rewarding psychoactive effects that might motivate abuse.

In a typical self-administration experiment, an animal presses a lever to activate a pump that delivers the drug directly into the animal’s bloodstream via an implanted catheter. The more drug an animal self-administers within a defined time frame, the greater the drug’s potential for abuse is likely to be. See also progressive ratio.

Self-administration studies also are often used to test whether a medication, anti-drug vaccine, or other treatment will reduce a drug’s rewarding effect and abuse liability. If the treatment is effective, treated animals will self-administer significantly less drug than untreated animals.

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