Faculty Collaboration Database

Assessing combined effects of varenicline and N-acetylcysteine on reducing nicotine seeking in rats. Addict Biol 2022 Mar;27(2):e13151

Date

03/02/2022

Pubmed ID

35229943

Pubmed Central ID

PMC10777539

DOI

10.1111/adb.13151

Scopus ID

2-s2.0-85125307551 (requires institutional sign-in at Scopus site)   2 Citations

Abstract

Nicotine addiction is a chronic relapsing brain disorder, and cigarette smoking is the leading cause of preventable death in the United States. Currently, the most effective pharmacotherapy for smoking cessation is Varenicline (VRN), which reduces both positive and negative reinforcement by nicotine. Clinically, VRN attenuates withdrawal symptoms and promotes abstinence, but >50% of smokers relapse within 3 months following a quit attempt. This may indicate that VRN fails to ameliorate components of nicotine-induced neuroplasticity that promote relapse vulnerability. Animal models reveal that glutamate dysregulation in the nucleus accumbens is associated with nicotine relapse. N-acetylcysteine (NAC) normalizes glutamate transmission and prolongs cocaine abstinence. Thus, combining VRN and NAC may promote and maintain, respectively, nicotine abstinence. In rats, we found that VRN effectively reduced nicotine self-administration and seeking in early abstinence, but not seeking later in abstinence. In contrast, NAC reduced seeking only later in abstinence. Because VRN and NAC are sometimes associated with mild adverse effects, we also evaluated a sequential approach combining subthreshold doses of VRN during self-administration and early abstinence with subthreshold doses of NAC during late abstinence. As expected, subthreshold VRN did not reduce nicotine intake. However, subthreshold VRN and NAC reduced seeking in late abstinence, suggesting a combined effect. Overall, our results suggest that combining subthreshold VRN and NAC is a viable and drug-specific approach to promote abstinence and reduce relapse while minimizing adverse effects. Our data also suggest that different components and time points in addiction engage the different neurocircuits targeted by VRN and NAC.

Author List

Nall RW, Beloate LN, Meyerink ME, Penaloza T, Doolittle J, Froeliger B, Kalivas PW, Garcia-Keller C

Author

Constanza Garcia Keller PhD Assistant Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acetylcysteine
Animals
Nicotine
Rats
Smoking Cessation
Tobacco Use Disorder
Varenicline