Persistent cognitive and affective alterations at late withdrawal stages after long-term intermittent exposure to tobacco smoke or electronic cigarette vapour: Behavioural changes and their neurochemical correlates.

Introduction:
This manuscript presents a study on the persistent cognitive and affective alterations that occur during late withdrawal stages after long-term intermittent exposure to tobacco smoke or electronic cigarette (e-CIG) vapour in Balb/c mice. The study investigates the behavioural and neurochemical effects of withdrawal for up to 90 days after seven weeks’ intermittent exposure to e-CIG vapour or cigarette smoke (CIG).

Key Points:

* The withdrawal of e-CIG and CIG induced early behavioural alterations such as spatial memory deficits, increased anxiety, and compulsive-like behaviour that persisted for 60-90 days.
* attention-related and depression-like behaviours appeared only 15-30 days after withdrawal and persisted for as long as up to 90 days.
* at hippocampal level, the withdrawal-induced changes in the levels of aMPa receptor Glua1 and Glua2/3 subunits, PSD 95 protein, corticotropin-releasing factor (Crf) and Crf receptor 1 (CrfR1) mRNa were biphasic.
* aMPa receptor subunit and PSD95 protein levels initially remained unchanged and decreased after 60-90 days, whereas Crf/CrfR1 mRNa levels initially increased and then markedly decreased after 60 days.
* Late reductions in Crf/CrfR1 mRNa levels correlated with the behavioural impairments, particularly the appearance of depression-like behaviours.
* e-CIG vapour and CIG smoke induce similar, in terms of time course and severity, behavioural and neurochemical alterations during both dependence and withdrawal phases.

Main Message:
The findings of this study suggest that major behavioural and neurochemical alterations persist or even first appear late after the withdrawal of chronic CIG smoke or e-CIG vapour exposure. These results underline the importance of conducting similar studies in humans, including e-CIG vapers, to better understand the long-term effects of e-CIG use and support evidence-based public health policies.

Ponzoni L, Braida D, Carboni L, et al. Persistent cognitive and affective alterations at late withdrawal stages after long-term intermittent exposure to tobacco smoke or electronic cigarette vapour: Behavioural changes and their neurochemical correlates. Pharmacol Res. 2020;158:104941. doi:10.1016/j.phrs.2020.104941