Alcohol vapor exposure differentially impacts mesocorticolimbic cytokine expression in a sex-, region-, and duration-specific manner

- Acute and subchronic alcohol vapor increases TNFα mRNA in the BLA, NAc, and VTA.
- TNFα mRNA remains elevated in the NAc following chronic alcohol vapor exposure.
- Males exhibit enhanced alcohol-induced IL-6 mRNA expression in the NAc and VTA.
- CCL2 mRNA is increased in the male BLA and VTA only after chronic alcohol vapor.

Alcohol exposure elicits the production of cytokines that regulate the host response to infection, immunity, inflammation, and trauma. Although increased production of pro-inflammatory cytokines has been linked to symptoms of alcoholism, few studies have evaluated whether cytokine expression changes across the development of alcohol dependence, or whether these changes are region and/or sex specific. In the present study, we subjected adult male and female rats to different regimens of alcohol vapor exposure (acute, subchronic, or chronic) and measured relative mRNA expression for tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), and chemokine (C-C motif) ligand 2 (CCL2) in reward-related brain regions. Results indicated that acute alcohol exposure increased TNFα mRNA expression in the basolateral amygdala (BLA), nucleus accumbens (NAc), and ventral tegmental area (VTA), whereas IL-6 expression was increased in the VTA, NAc, and ventromedial prefrontal cortex (vmPFC) only in males. After subchronic exposure (1 week daily intermittent exposure, 14 h on:10 h off), TNFα expression remained elevated in the BLA, NAc, and VTA, while IL-6 expression was reduced in the male vmPFC. Chronic alcohol exposure (6 week daily intermittent exposure, 14 h on: 10 h off) increased TNFα mRNA expression in the NAc and increased IL-6 mRNA in the vmPFC and NAc. Interestingly, chronic alcohol exposure also robustly increased CCL2 mRNA expression in the BLA and VTA in males but not females. Thus, alcohol vapor exposure elicits sex-, region-, and duration-specific cytokine alterations that may contribute to differences in the manifestation and progression of symptoms of alcohol dependence in male and female populations.