Glossary of terms

Behavior TermDefinition
ABA context-induced reinstatementA behavior procedure in which laboratory animals are first trained to self-administer a drug in an environment (termed context A) associated with a specific set of background stimuli (e.g., operant chamber fan, time of day, visual cues, tactile stimuli, olfactory stimuli). Lever pressing is then extinguished in a different environment (termed context B) with a different set of background stimuli. During reinstatement testing under extinction conditions, exposure to context A previously paired with the drug reinstates operant responding. The procedure is based on the ABA renewal procedure that has been used to assess the role of contexts in resumption of conditioned responses to aversive and appetitive cues after extinction.
Community reinforcement approachA learning-based treatment developed for alcohol addiction in the 1970s and combined with contingency management for other addictions in the 1990s. Its goal is to substitute drug use with nondrug social rewards (family support, employment) contingent on decrease or cessation of drug use.
Contingency managementA learning-based treatment in which abstinence is maintained by providing nondrug rewards (monetary vouchers, prizes, or other incentives) given promptly and predictably in exchange for negative drug tests.
Daun02 chemogenetic inactivation procedureA method to selectively disrupt the function of behaviorally activated neurons. This method enables investigation of whether “neuronal ensembles” (subsets of activated neurons) are involved learned behaviors. Selective inactivation is performed by injecting a prodrug, Daun02, into the brains of Fos-lacZ transgenic rats that express β-galactosidase in strongly activated neurons. β-Galactosidase converts Daun02 into daunorubicin, which reduces neuronal excitability.
Discrete cuesNeutral stimuli (e.g., light, tone) that become conditioned reinforcers after repeated temporal pairing with drug infusions and effects during self-administration training. In studies on discrete cue–induced reinstatement, rats are trained to self-administer a drug or food; each reward delivery is temporally paired with the discrete cue. Lever pressing is then extinguished in the absence of the discrete cue. During reinstatement testing, exposure to the discrete cue, which is earned contingently by responding on the drug-associated lever, reinstates drug or food seeking.
Drug cravingA subjective state that refers to a strong desire to consume an addictive drug. In animal models, craving is often used to describe the motivation state associated with drug taking and seeking in a manner analogous to the use of hunger as the motivational state associated with taking and seeking food rewards or fear as the motivation state associated with freezing induced by aversive stimuli such as high-intensity foot shock or predator odor.
Escalation modelAn animal model of escalation of drug intake in which rats are given continuous extended access to drug (6–12 h per day). Under these experimental conditions, most rats increase their drug intake over time. In the escalation model, drug intake and drug brain levels are relatively constant during the daily sessions.
ExtinctionA decrease in the frequency or intensity of learned responses after the removal of the reinforcer (e.g., food, drug) that has reinforced the learning.
Fixed-ratio reinforcement scheduleA schedule of reinforcement in which a reinforcer is presented upon the completion of a fixed number of responses.
Forced abstinenceA term refers to experimental conditions in which abstinence after drug self-administration is experimenter-imposed. In animal models, forced abstinence can be achieved by 1) extinction training in the drug self-administration context or a nondrug context or (2) keeping the subjects in their home cage during the abstinence period.
Incubation of drug cravingA hypothetical motivational process inferred from the findings of time-dependent increases in nonreinforced drug seeking during abstinence from drug self-administration in rats.
Intermittent-access drug self-administration modelAn animal model of intermittent access of drug intake in which cycles of drug availability (typically 5 min ON, 25 min OFF for 6–8 h per day) are presented within a daily session. In the intermittent-access model, drug intake and drug brain levels fluctuate between peaks and troughs during the daily sessions.
Neuronal ensemblesSpecific patterns of synchronously activated neurons that are hypothesized to encode highly specific and complex information underlying learning, memory, motivation, and other psychologic processes. Neuronal ensembles have been traditionally studied with in vivo electrophysiology using multielectrode recordings, which provide temporal information on neuronal activity patterns (i.e., when the neurons are activated in the brain during behavior). The immunohistochemical detection of IEGs such as Fos or Arc can also be used to study neuronal ensembles by providing information on the spatial expression patterns of behaviorally relevant activated neurons (i.e., where the neuronal ensemble neurons are in the brain).
Postdictive validityThe ability of a laboratory model to retrospectively demonstrate an established human phenomenon. This typically refers to the demonstration that a medication previously shown to be effective in the treatment of a human disease is also effective in the animal model of the disease.
Predictive validityThe extent to which laboratory-animal behavior induced by an experimental manipulation predicts human behavior induced by a similar event in the modeled condition. The concept often refers to a model’s ability to identify new treatments that are effective in humans.
Progressive-ratio reinforcement scheduleA schedule of reinforcement in which a reinforcer is only presented upon the completion of a set number of responses. The number of required responses progressively increases after each presented reinforcement.
ReacquisitionThe resumption of the original learned response when the reinforcer (operant or classic) is reintroduced after extinction.
Reinstatement modelThe most commonly used animal model of drug relapse. In the context of addiction research, reinstatement refers to the resumption of drug seeking after extinction of the drug-reinforced responding. The resumption is typically induced by exposure to priming drug injections, drug-associated cues, drug-associated contexts, or stressors.
RelapseResumption of drug-taking behavior during self-imposed (voluntary) or forced abstinence in humans and laboratory animals.
RenewalThe recovery of extinguished conditioned behavior, which can occur when the context is changed after extinction; renewal often occurs when the subject returns to the learning (training) environment (context) after extinction of the conditioned response in a different context.
Retro-DREADD dual-virus approachA double-virus method that allows for selective inhibition or activation of defined neuronal projections. The method comprises the combined use of a CRE-recombinase–expressing CAV2 or AAV injected into a terminal region of interest and a second AAV virus that contains a DIO version of an inhibitory or an excitatory DREADD injected into the cell body region. CAV2 or the AAV retrogradely infects projection neurons, resulting in projection-specific expression of the DREADD receptor. During behavioral testing, injections of the otherwise inactive drugs like CNO or Sal B result in selective activation or inhibition (in the case of CNO) or selective inhibition (in case of Sal B) of the neuronal projection of interest.
Second-order reinforcement scheduleA reinforcement schedule in which completion of the response requirements of one schedule (the unit schedule) is treated as a unitary response that is reinforced according to another schedule.
Spontaneous recoveryThe resumption of the extinguished conditioned response that occurs after time has passed after the conclusion of extinction.
Three-criteria DSM-IV modelAn animal model of drug intake that is based on three DSM-IV criteria used in humans to identify addicted rats (Deroche-Gamonet et al., 2004). After self-administration training, the model evaluates three behaviors based on DSM-IV criteria: persistent drug seeking during periods when drug is not available, high motivation to self-administer the drug (progressive-ratio responding), and willingness to take drug despite adverse consequences (foot-shock punishment). Next, an addiction score (scale 0–3) based on the subjects’ percentile on each measure’s distribution is calculated. Approximately 20% of rats meet all three addiction criteria.
Voluntary abstinenceA term used to refer to experimental conditions in which the self-administered drug is available in the self-administration chamber but the laboratory animal either stops or significantly decreases the drug self-administration behavior. In animal models, voluntary abstinence can be achieved by introducing 1) mild foot-shock punishment after the drug-reinforced operant response, 2) an electric barrier that delivers mild shock near the drug-paired lever, 3) mutually exclusive alternative palatable food reward, and 4) mutually exclusive alternative social reward (see text).
  • AAV, adeno-associated virus; CAV2, canine adenovirus-2; CNO, Clozapine N Oxide; Cre recombinase, a tyrosine recombinase enzyme derived from the P1 bacteriophage; DIO, double floxed inverse open reading frame; IEG, immediate early gene; Sal B, Salvinorin B.