Continuous nicotine exposure does not affect resurgence of alcohol seeking in rats

Abstract

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 translated into preventative utility. One potentially important factor, concurrent nicotine use, has not been well investigated as a causal factor in relapse for alcohol use disorder. Nicotine increases the value of other stimuli in the environment and may increase the value of alcohol. If nicotine increases the value of alcohol, then nicotine use during and after treatment may make relapse more probable. In the current study, we investigated the effect of continuous nicotine exposure (using osmotic minipumps to deliver nicotine or saline, depending on group, at a constant rate for 28 days) on resurgence of alcohol seeking in rats. Resurgence is a type of relapse preparation that consists of three phases: Baseline, Alternative Reinforcement, and Resurgence Testing. During Baseline, target responses produced a dipper of alcohol. During Alternative Reinforcement, target responses were extinguished and responses on a chain produced a chocolate pellet. During Resurgence Testing, responses on the chain were also extinguished and a return to responding on the target lever was indicative of resurgence. Multilevel modeling was used to analyze the effect of nicotine on resurgence. Both the nicotine and saline group showed resurgence of alcohol seeking, but there was no difference in the degree of resurgence across groups. Future directions could involve testing alternative drug delivery techniques.

Resurgence of punishment-suppressed cocaine seeking in rats.

“…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).…”

“…Resurgence of drug seeking is often studied in animals using a three-phase procedure (Craig, Nall, Madden, & Shahan, 2016; Frye et al, 2018; Nall, Craig, Browning, & Shahan, 2018; Quick, Pyszczynski, Colston, & Shahan, 2011; Shahan, Craig, & Sweeney, 2015). In Phase 1, animals are trained to perform a target response to earn drug reinforcement.…”

“…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 (Nall et al, 2018; 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).…”

Drug versus non‐drug behaviors: A dual‐reward model of sex differences and neurobiological mechanisms in rats

“…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.…”

Associative processes in addiction relapse models: A review of their Pavlovian and instrumental mechanisms, history, and terminology

“…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].…”