Effect of chronic vapor nicotine exposure on affective and cognitive behavior in male mice

TL;DR

This study examines how chronic nicotine vapor exposure affects behavior and cognition in male mice, creating a model similar to human nicotine use.

Contribution

The study introduces a validated ENDS-based model for chronic nicotine exposure in mice, mimicking human smoking patterns.

Findings

Chronic nicotine exposure led to impairments in cognitive behavior in mice.

Nicotine and cotinine plasma levels varied with different inter-vape intervals.

Behavioral changes were observed in measures like locomotor activity and pain hypersensitivity.

Abstract

Nicotine use is a leading cause of preventable deaths worldwide, and most of those who attempt to quit will relapse. While electronic cigarettes and other electronic nicotine delivery systems (ENDS) were presented as a safer alternative to traditional cigarettes and promoted as devices to help traditional tobacco smokers reduce or quit smoking, they have instead contributed to increasing nicotine use among youths. Despite this, ENDS also represent a useful tool to create novel preclinical animal models of nicotine exposure that more accurately represent human nicotine use. In this study, we validated a chronic, intermittent, ENDS-based passive vapor exposure model in mice, and then measured changes in multiple behaviors related to nicotine abstinence. First, we performed a behavioral dose curve to investigate the effects of different nicotine inter-vape intervals on various measures including body weight, locomotor activity, and pain hypersensitivity. Next, we performed a pharmacokinetic study to measure plasma levels of nicotine and cotinine following chronic exposure for each inter-vape interval. Finally, we utilized a behavior test battery at a single dosing regimen that produces blood levels equivalent to human smokers in order to characterize the effects of chronic nicotine, vehicle, or passive airflow and identified nicotine-induced impairments in cognitive behavior.