Alcohol and nicotine are often used together, and there is a high rate of co-occurrence between alcohol and nicotine addiction. Most animal models studying alcohol and nicotine interactions have utilized passive drug administration, which may not be relevant to human co-addiction. In addition, the interactions between alcohol and nicotine in female animals have been understudied, as most studies have used male animals. To address these issues, we developed models of alcohol and nicotine co-consumption in male and female mice that utilized voluntary, oral consumption of unsweetened alcohol, nicotine and water. We first examined drug consumption and preference in single-drug, sequential alcohol and nicotine consumption tests in male and female C57BL/6 and DBA/2J mice. We then tested chronic continuous and intermittent access alcohol and nicotine co-consumption procedures. We found that male and female C57BL/6 mice readily co-consumed unsweetened alcohol and nicotine. In our continuous co-consumption procedures, we found that varying the available nicotine concentration during an alcohol abstinence period affected compensatory nicotine consumption during alcohol abstinence, and affected rebound alcohol consumption when alcohol was re-introduced. Consumption of alcohol and nicotine in an intermittent co-consumption procedure produced higher alcohol consumption levels, but not nicotine consumption levels, compared with the continuous co-consumption procedures. Finally, we found that intermittent alcohol and nicotine co-consumption resulted in physical dependence. Our data show that these voluntary co-consumption procedures can be easily performed in mice and can be used to study behavioral interactions between alcohol and nicotine consumption, which may better model human alcohol and nicotine co-addiction.
Alcohol and nicotine addiction are frequently co-morbid. The nicotinic acetylcholine receptors (nAChRs) are critical for both alcohol and nicotine addiction mechanisms, since nAChR drugs that reduce nicotine consumption have been shown to also reduce alcohol consumption. Sazetidine-A, a pre-clinical nAChR drug with agonist and desensitizing effects at α4β2 and α7 nAChRs, has been reported to reduce alcohol consumption and nicotine self-administration in rats when administered at high doses. However, this effect has not been replicated in mice. In this study, we examined the effect of sazetidine-A on alcohol and nicotine consumption in male and female mice utilizing voluntary oral consumption procedures previously developed in our lab. We found that sazetidine-A (1 mg/kg, i.p) reduced overnight alcohol consumption, but did not affect nicotine consumption when presented either alone or concurrently with alcohol. Sazetidine-A did not reduce water or saccharin consumption at any dose tested. In a chronic co-consumption experiment in which either alcohol or nicotine was re-introduced after one week of forced abstinence, sazetidine-A attenuated post-abstinence consumption of alcohol but not nicotine. Sazetidine-A also significantly reduced alcohol consumption in an acute, binge drinking-in-the-dark procedure. Finally, we tested the effect of sazetidine-A on alcohol withdrawal, and found that sazetidine-A significantly reduced handling-induced convulsions during alcohol withdrawal. Collectively, these data suggest a novel role for the nAChR targets of sazetidine-A in specifically mediating alcohol consumption, separate from the involvement of nAChRs in mediating nicotine consumption. Delineation of this pathway may provide insight into novel therapies for the treatment of alcohol use disorders.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.