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Alcohol is the most commonly used drug in the United States and alcohol abuse can lead to alcohol use disorder. Alcohol use disorder is a persistent condition and relapse rates following successful remission are high. Many factors have been associated with relapse for alcohol use disorder, but identification of these factors has not been well trans...
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The purpose of our article is to contribute to the understanding of the mechanisms that intervene in determining the success of abstinence in case of persons suffering from alcohol use disorder (PAUD), a phenomenon that is poorly investigated, but, obviously, extremely important. Based on the database containing 273 Romanian PAUDs, split in three c...
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... Due to the large difference in active responding and reinforcers earned between cocaine and food options during self-administration, all subsequent analyses were performed on proportions of baseline responding (see Table 1 for raw responses and proportional transformations throughout the experiment). Proportions of baseline were calculated by dividing the response count on a given session by the mean of the response count from the last three sessions of self-administration (e.g., Frye et al., 2018). Thus, for each rat cocaine responses were normalized to cocaine responding during self-administration, and food responses were normalized to food responding during self-administration. Figure 2C shows proportion of baseline responding during reinforcer competition for male and female rats. ...
Substance Use Disorders (SUDs) are an impactful problem characterized by chronic relapse and engagement in drug‐related behaviors at the expense of non‐drug behaviors. Brain regions implicated in drug and non‐drug‐related behaviors often overlap, complicating investigations of neurobiological mechanisms underlying SUDs. Here we presented a within‐subject model for studying self‐administration, reinforcer competition, extinction, and cued reinstatement of cocaine‐ and food‐seeking in rats. Due to differences in cocaine‐ and food‐reinforced behavior, we transformed data to proportions of baseline, revealing increased resistance to extinction and disproportionately greater cued reinstatement of cocaine seeking relative to food seeking. Consistent with previous reports, females showed greater preference for cocaine reinforcement than males, though these findings failed to reach statistical significance. To demonstrate the model's utility for investigating neurobiological mechanisms, we included proof‐of‐concept calcium imaging data demonstrating the utility of the behavioral model for detecting cellular activity patterns associated with cocaine‐ and food‐seeking behaviors. Future studies utilizing this model should improve understanding of the development and expression of pathological behaviors characteristic of SUDs in humans, sex differences in these behaviors, and their neurobiological correlates. Thus, the model has utility for improving understanding of SUDs, leading to novel treatments to reduce the pathological behaviors associated with SUDs.
... The resurgence effect suggests that there is potential for relapse when therapy concludes and incentives are withdrawn [14] which is known to occur [73]. Animal studies have shown that resurgence occurs when drugs such as alcohol or cocaine are used as reinforcers [74][75][76]. One potential point of contention is that Bouton and colleagues have conceptualised resurgence as renewal due to a novel context ('C') that is distinct from both the acquisition context ('A') and the extinction context ('B'), also known as ABC renewal [14]. ...
Animal models of relapse to drug-seeking have borrowed heavily from associative learning approaches. In studies of relapse-like behaviour, animals learn to self-administer drugs then receive a period of extinction during which they learn to inhibit the operant response. Several triggers can produce a recovery of responding which form the basis of a variety of models. These include the passage of time (spontaneous recovery), drug availability (rapid reacquisition), extinction of an alternative response (resurgence), context change (renewal), drug priming, stress, and cues (reinstatement). In most cases, the behavioural processes driving extinction and recovery in operant drug self-administration studies are similar to those in the Pavlovian and behavioural literature, such as context effects. However, reinstatement in addiction studies have several differences with Pavlovian reinstatement, which have emerged over several decades, in experimental procedures, associative mechanisms, and terminology. Interestingly, in cue-induced reinstatement, drug-paired cues that are present during acquisition are omitted during lever extinction. The unextinguished drug-paired cue may limit the model’s translational relevance to cue exposure therapy and renders its underlying associative mechanisms ambiguous. We review major behavioural theories that explain recovery phenomena, with a particular focus on cue-induced reinstatement because it is a widely used model in addiction. We argue that cue-induced reinstatement may be explained by a combination of behavioural processes, including reacquisition of conditioned reinforcement and Pavlovian to Instrumental Transfer. While there are important differences between addiction studies and the behavioural literature in terminology and procedures, it is clear that understanding associative learning processes is essential for studying relapse.
... Resurgence is evidenced by an increase in target responding following the removal of alternative reinforcement in Phase 3 (i.e., resurgence of drug seeking). This procedure has been used previously to demonstrate resurgence of cocaine Quick et al., 2011;Shahan, Craig, & Sweeney, 2015) and alcohol (Frye et al., 2018;Nall et al., 2018;Podlesnik, Jimenez-Gomez, & Shahan, 2006) seeking in rats, leading some to suggest that the animal model of resurgence may be useful for studying relapse following the loss of alternative reinforcement in human treatment settings (Marchant, Li, & Shaham, 2013;Peck & Ranaldi, 2014;Winterbauer & Bouton, 2010). ...
... The procedure developed in Experiment 1 evaluated resurgence induced by loss of alternative reinforcement in Phase 3 under conditions where cocaine-seeking responses had no consequences. This is advantageous for making comparisons to other resurgence procedures (Frye et al., 2018;Nall et al., 2018Nall et al., , 2019Quick et al., 2011;Shahan et al., 2015) as well as other procedures that have examined relapse of previously punished drug seeking (Marchant, Khuc, Pickens, Bonci, & Shaham, 2013;Nall et al., 2019;Panlilio et al., 2003;Pelloux et al., 2018). However, humans are not likely to experience extinction of drug seeking following treatment with alternative reinforcement (Marchant, Li, et al., 2013;Panlilio et al., 2005). ...
Alternative reinforcement-based treatments are among the most effective for reducing substance abuse. However, relapse often occurs when alternative reinforcement ends. Relapse following the loss of alternative reinforcement is called resurgence. An animal model has been used to study basic factors that may ultimately reduce resurgence but uses drug unavailability (i.e., extinction) to reduce drug seeking. In humans, drug abstinence is thought to be a product of aversive consequences associated with drug use rather than extinction. This discrepancy is important because the environmental and neurobiological factors involved in relapse may differ between punished and extinguished behavior. Experiment 1 evaluated resurgence of previously punished cocaine seeking. In Phase 1, rats earned cocaine for pressing levers. In Phase 2, cocaine remained available, but lever pressing also produced mild foot shocks while an alternative response produced food pellets for 1 group but not for another group. In Phase 3, alternative reinforcement and punishment were removed and resurgence of cocaine seeking occurred only in rats previously exposed to alternative reinforcement. In Experiment 2, resurgence was evaluated similarly, except that consequences of cocaine seeking (i.e., punishment and cocaine) remained available during Phase 3. Resurgence did not occur in either group during Experiment 2. The animal models of resurgence developed herein could increase translational utility and improve examination of the environmental and neurobiological factors underlying resurgence of drug seeking. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Unlabelled:
Resurgence is the return of a previously reinforced response as conditions worsen for an alternative response, such as the introduction of extinction, reductions in reinforcement, or punishment. As a procedure, resurgence has been used to model behavioral treatments and understand behavioral processes contributing both to relapse of problem behavior and flexibility during problem-solving. Identifying existing procedural and analytic methods arranged in basic/preclinical research could be used by basic and preclinical researchers to develop novel approaches to study resurgence, whereas translational and clinical researchers could identify potential approaches to combating relapse during behavioral interventions. Despite the study of resurgence for over half a century, there have been no systematic reviews of the basic/preclinical research on resurgence. To characterize the procedural and analytic methods used in basic/preclinical research on resurgence, we performed a systematic review consistent with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). We identified 120 articles consisting of 200 experiments that presented novel empirical research, examined operant behavior, and included standard elements of a resurgence procedure. We reported prevalence and trends in over 60 categories, including participant characteristics (e.g., species, sample size, disability), designs (e.g., single subject, group), procedural characteristics (e.g., responses, reinforcer types, control conditions), criteria defining resurgence (e.g., single test, multiple tests, relative to control), and analytic strategies (e.g., inferential statistics, quantitative analysis, visual inspection). We make some recommendations for future basic, preclinical, and clinical research based on our findings of this expanding literature.
Supplementary information:
The online version contains supplementary material available at 10.1007/s40614-022-00361-y.
Substances of abuse have the potential to cause addiction, habituation or altered consciousness. Most of the research on these substances focuses on addiction, and is carried out through observational and clinical studies on humans, or experimental studies on animals. The transposition of the EU Directive 2010/63 into Italian law in 2014 (IT Law 2014/26) includes a ban on the use of animals for research on substances of abuse. Since then, in Italy, public debate has continued on the topic, while the application of the Article prohibiting animal research in this area has been postponed every couple of years. In the light of this debate, we briefly review a range of methodologies - including animal and non-animal, as well as patient or population-based studies - that have been employed to address the biochemical, neurobiological, toxicological, clinical and behavioural effects of substances of abuse and their dependency. We then discuss the implications of the Italian ban on the use of animals for such research, proposing concrete and evidence-based solutions to allow scientists to pursue high-quality basic and translational studies within the boundaries of the regulatory and legislative framework.
