Anxiety-like behavior in rats during periods of abstinence following E-cigarette vapor and cigarette smoke exposure: Role of inflammatory cytokines and glutamate receptors

Abstract

Prolonged exposure to cigarette smoke induces changes in the glutamatergic systems as well as neuroinflammation. We examined E-cigarette vapor and cigarette smoke effects on inflammatory cytokines and metabotropic glutamate receptors. Furthermore, we investigated the behavioral changes related to E-cigarette vapor and cigarette smoke exposure through utilizing open field (OF), elevated plus maze (EPM) and light/dark (LD) tests. Male Sprague-Dawley rats were randomly assigned to three experimental groups: Control, E-cigarette, and Cigarettes groups. Exposure to either E-cigarette vapor or cigarette smoke exposure was performed for 2 hr/day, 5 days/week, for 60 days. Behavioral tests were conducted every two weeks, 24 hr after exposure, during periods of abstinence. Anxiety-like behaviors were increased following repeated periods of abstinence from E-cigarette vapor or cigarette smoke. E-cigarette vapor and cigarette smoke elevated the relative mRNA expression of nuclear factor ĸB (Nf-ĸB), interleukin 6 (Il-6), and metabolic glutamate receptor 5 (mglur5) and reduced expression of interleukin 1β (Il-1β), tumor necrosis α (Tnf-α), and metabolic glutamate receptor 2 (mglur2) in prefrontal cortex (PFC) and nucleus accumbens (NAc). Moreover, no effect was observed on nuclear factor erythroid 2 (Nrf2), metabolic glutamate receptor 1 (mglur1), or metabolic glutamate receptor 3 (mglur3) expression. E-cigarette vapor and cigarette smoke exposure can lead to abstinence-induced anxiety-like behavior partially through molecular changes in the PFC and NAc.