Rodent models for nicotine withdrawal

Abstract

Background: Animal models are critical to improve our understanding of the neuronal mechanisms underlying nicotine withdrawal. Nicotine dependence in rodents can be established by repeated nicotine injections, chronic nicotine infusion via osmotic minipumps, oral nicotine intake, tobacco smoke exposure, nicotine vapor exposure, and e-cigarette aerosol exposure. The time course of nicotine withdrawal symptoms associated with these methods has not been reviewed in the literature. Aim: The goal of this review is to discuss nicotine withdrawal symptoms associated with the cessation of nicotine, tobacco smoke, nicotine vapor, and e-cigarette aerosol exposure in rats and mice. Furthermore, age and sex differences in nicotine withdrawal symptoms are reviewed. Results: Cessation of nicotine, tobacco smoke, nicotine vapor, and e-cigarette aerosol exposure leads to nicotine withdrawal symptoms such as somatic withdrawal signs, changes in locomotor activity, anxiety- and depressive-like behavior, learning and memory deficits, attention deficits, hyperalgesia, and dysphoria. These withdrawal symptoms are most pronounced within the first week after cessation of nicotine exposure. Anxiety- and depressive-like behavior, and deficits in learning and memory may persist for several months. Adolescent (4–6 weeks old) rats and mice display fewer nicotine withdrawal symptoms than adults (>8 weeks old). In adult rats and mice, females show fewer nicotine withdrawal symptoms than males. The smoking cessation drugs bupropion and varenicline reduce nicotine withdrawal symptoms in rodents. Conclusion: The nicotine withdrawal symptoms that are observed in rodents are similar to those observed in humans. Tobacco smoke and e-cigarette aerosol contain chemicals and added flavors that enhance the reinforcing properties of nicotine. Therefore, more valid animal models of tobacco and e-cigarette use need to be developed by using tobacco smoke and e-cigarette aerosol exposure methods to induce dependence.

Withdrawal: A key consideration in evaluating whether highly processed foods are addictive

“…27 Notably, the timeframe of emergence of withdrawal symptoms observed in these studies (within 24-36 h after last consumption of HP foods) mirrors the timeframe observed in animal studies of withdrawal from other addictive substances. 43,44 Another core component of withdrawal demonstrated by animal models is enhanced motivational drive to consume the substance, which can also be conceptualized as craving. 24 Animals exhibit craving for a substance by engaging in behavioral indicators that have previously been paired with administration of the substance (e.g., nose pokes and lever presses).…”

“…Animals demonstrate affective and physical symptoms during withdrawal from several addictive substances, including nicotine, alcohol, and cannabis 43–45 . Most animal models of substance withdrawal have been investigated in rodents 46 .…”

Nicotine self-administration and ERK signaling are altered in RasGRF2 knockout mice

“…In the SA study outlined here, both male and female RasGRF2 KO and WT mice were used to identify potential sex-dependent differences in nicotine SA and its mediation by RasGRF2. Previous studies of nicotine SA in rodents have demonstrated either increased intake in males, no differences in intake between males and females, or higher intake in females relative to males (Donny et al, 2000;Feltenstein et al, 2012;Bernardi et al, 2016;Flores et al, 2019;Chen et al, 2020;Chellian et al, 2021;Leyrer-Jackson et al, 2021). Here we found no sexdependent differences in nicotine intake in WT mice; however, we did not measure other specific aspects of nicotine SA that may differ among males and females, such as motivation, extendedaccess procedures, reinstatement, and treatment effectiveness, which are likely relevant to clinical outcomes in humans.…”

Nicotine modulation of the lateral habenula/ventral tegmental area circuit dynamics: An electrophysiological study in rats

“…Nevertheless, more doses of nicotine should be tested to see how the LHb/VTA dynamics would change. Finaly, our experiments were performed in male rats but a growing number of studies reports genderspecific effects of nicotine that need to be addressed in future studies (Chellian et al, 2021;Cruz et al, 2021;O'Dell & Torres, 2014).…”