TABLE 1

Glossary of the key terms used in this review

TermDefinition
Addition-like featureThe expression of a behavior in an animal that resembles a criterion, or symptom, of SUD in humans as defined by the DSM-5 (American Psychiatric Association, 2013). Some of the more commonly modeled features include escalation of drug intake over time, binge/abstinent patterns of drug intake, physical dependence, an enhanced motivation to obtain the drug, compulsive drug use despite adverse consequences, preference for the drug over a nondrug rewards, and enhanced drug-craving/vulnerability to relapse (Lynch 2018).
Addition-like phenotypeThe expression in an animal of ≥1 characteristics (or addiction-like features) that resemble features of SUD in humans as defined by the DSM-5. For example, the development of an enhanced motivation for the drug has been used to define the development of an addiction-like phenotype since, as in humans, once this feature emerges, it appears to represent a relatively permanent shift to a higher motivational state (Lynch 2018).
Acquisition procedureA procedure that uses a set of performance criteria to define the time-point when an animal has learned a new behavior, such as lever pressing to obtain infusions of a drug. Acquisition procedures can be a strong tool for investigating individual differences in sensitivity to the reinforcing effects of a drug. These effects are ideally studied under low-dose conditions and the question asked is, which animals can detect the reinforcing effects of this low dose of the drug? A faster speed of acquisition and/or greater percent group acquisition is then used to define an enhanced vulnerability to substance use (Lynch et al., 2010).
Animal model of substance useA model used to assess initial vulnerability to use addictive drugs. Short-access drug self-administration procedures (1–2 h/d access) are commonly used and focus on rates and/or percent group acquisition of drug self-administration, maintenance levels of drug use, or motivation to obtain the drug, as assessed using a progressive-ratio schedule or a within-session threshold procedure, following acquisition.
Animal model of substance use disorderA model that has been validated to induce an addiction-like phenotype in animals like that observed in humans with SUD. Extended-access drug self-administration procedures (≤6 h/d access) are the gold-standard for inducing addiction-like features in animals (Lynch 2018).
Binge/abstinent patternA binge-abstinent of pattern of drug self-administration is characterized by cycles of heavy/prolonged periods of drug use (binge intake) separated by periods of self-imposed abstinence.
Choice procedureA procedure used to determine percent choice, or preference, for one reinforcer over another (or for different magnitudes of a reinforcer). Choice procedures can be a powerful approach for determining individual differences in vulnerability to developing a preference for the drug over other nondrug rewards, such as a highly palatable food reward, and for determining potential interventions that reverse a drug preference back to a nondrug one.
Compulsive drug useA core feature of addiction in humans that is modeled in animals using punishment or choice procedures. The development of this addiction-like feature has been defined as continued drug use despite adverse consequences (e.g., coincident shock) or an exclusive choice (>90%) of the drug over an alternative nondrug reward (Lynch 2018). This addiction-like feature emerges following abstinence l (≥7 days) from extended-access self-administration and the magnitude of its expression increases with longer periods of abstinence (Towers et al., 2021).
Enhanced motivation to obtain the drugA core feature of addiction in humans that is modeled in animals using either a progressive ratio schedule or the threshold procedure. This feature has been defined as ≥15% increase in motivation for the drug relative to short-access controls or baseline prior to extended-access self-administration and abstinence (Lynch 2018). This addiction-like feature emerges following abstinence (≥7 days) from extended-access self-administration and the magnitude of its expression increases with longer periods of abstinence (Towers et al., 2021).
Enhanced drug-craving/vulnerability to relapseA core feature of addiction in humans that is modeled in animals using an extinction/reinstatement procedure or a cue-induced drug-seeking procedure. This addiction-like feature is typically assessed following extended-access self-administration and a period of protracted abstinence (>14 days) since these conditions induce high levels of drug-seeking relative to short-access controls and earlier abstinence time points. The expression of this addiction-like feature progressively increases, or incubates, over abstinence (Lynch 2018).
Escalation of drug intakeEscalation of drug intake occurs in animals given extended-access, but not short-access, to the drug and is characterized by a gradual increase in drug intake over time. It is ideally studied following acquisition of drug self-administration, to ensure that increases in intake are reflective of escalation rather than acquisition, and is thought to resemble the loss of control over drug intake feature observed in humans with SUD (Koob 2021).
Fixed-ratio scheduleA schedule of reinforcement in which a set number of responses (e.g., 1, 2, or 10) produce a reinforcer delivery, such as a drug infusion.
GenderThe characterization of women or men that is socially constructed and varies over time and between cultures (Committee on Understanding the Biology of Sex and Gender Differences 2001).
Incubation effectThe incubation effect refers to a progressive increase in drug-seeking from early to later periods of abstinence following extended-access self-administration. A similar phenomenon has also been reported in humans with SUD (Li et al., 2015) and is thought to reflect the development of an enhanced vulnerability to relapse. A similar incubation effect has also been observed for the development of other addiction-like features, including compulsive drug use and an enhanced motivation to obtain the drug (Gancarz-Kausch et al., 2014; Towers et al., 2021).
Intermittent-access procedureA drug self-administration procedure wherein access to the drug is intermittently available, such as in 5-min trials with unrestricted, fixed-ratio 1 access, or in discrete trials, With the most commonly used procedures, animals either have unrestricted, fixed-ratio 1 access to the drug infusions in 5-minute trials that initiate every 30 minutes for ≥6 h/d or to single infusions of the drug in discrete trials that initiate every 15 minutes 12–24 h/d (Fitch and Roberts 1993; Zimmer et al., 2012). Intermittent-access self-administration results in a binge-abstinent pattern of drug intake and spiking brain drug levels (Zimmer et al., 2012).
Long-access procedureA drug self-administration procedure that allows continuous, fixed-ratio 1 access to the drug for ≥6 h/d. This results in high levels of drug intake and an escalating pattern of drug use (Ahmed and Koob 1998).
Physical dependenceA core feature of addiction in humans that is assessed in animal models following chronic drug self-administration and defined by withdrawal-induced weight loss and somatic signs of withdrawal (e.g., abdominal constriction, salivation, ptosis, paw tremors; Lynch et al., 2010).
Preference for the drug over a nondrug rewardA core feature of addiction in humans that is modeled in animals using a choice procedure. The development of this addiction-like feature is defined as an exclusive choice (>90%) for the drug vs. a nondrug reward (Lynch 2018).
Progressive-ratio scheduleA schedule of reinforcement that requires the animal to emit an increasing amount of work (or lever pressing) to obtain each subsequent delivery of the drug within a session. The breakpoint, or the point that the animal stops responding, is used as a measure of motivation to obtain the drug.
Punishment procedurePunishment procedures decrease the probability of responding for the reinforcer. For example, when an aversive stimulus, such as electric shock, is paired with the delivery of the drug, drug-taking decreases. Punishment procedures have also been used to demonstrate compulsive use, a core feature of addiction in humans, wherein animals show a reduced sensitivity to punishment and continue to self-administer high levels of the drug.
Reinstatement procedureA model of relapse/drug-craving whereby the animal is tested on responding on a lever that was formerly associated with the drug under non-reinforced conditions (extinction), and once responding has reached a certain level of nonresponsiveness, the reinstatement of drug-seeking (responding on this same lever) is examined in response to presentations of drug-associated cues, a small “priming” dose of drug, or stress.
SexThe characterization of an individual as female or male according to their reproductive organs and functions derived from their chromosomal complement (generally XX for female and XY for male; Committee on Understanding the Biology of Sex and Gender Differences, 2001).
Short-access procedureA drug self-administration procedure wherein animals have access to the drug for 1–2 h/d. Such access results in relatively stable and low levels of drug intake from day to day.
Telescoping effectA phenomenon that describes a faster progression in females compared with males from initial drug use to meeting the criteria and/or seeking treatment of a SUD (Piazza et al., 1989).
Threshold procedureA procedure used to examine motivation to obtain a reinforcer. For example, the demand for a drug is measured by varying the price (response requirement) and the value (dose) of the drug within a session (Zimmer et al., 2012).