title: Alcohol vapor exposure differentially impacts mesocorticolimbic cytokine expression in a sex-, region-, and duration-specific manner.
abstract: 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 (1week daily intermittent exposure, 14h on:10h off), TNFα expression remained elevated in the BLA, NAc, and VTA, while IL-6 expression was reduced in the male vmPFC. Chronic alcohol exposure (6week 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.
authors.affiliation: Department of Integrative Physiology & Neuroscience, Washington State University, Pullman, WA 99614-7620, USA.
authors.forename: Lydia N
authors.initials: LN
authors.lastname: Baxter-Potter
authors.affiliation: Department of Psychology, Washington State University, Pullman, WA 99614-7620, USA.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Henricks
authors.affiliation: Department of Psychology, Washington State University, Pullman, WA 99614-7620, USA.
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Berger
authors.affiliation: Department of Psychology, Washington State University, Pullman, WA 99614-7620, USA.
authors.forename: Kennedy V
authors.initials: KV
authors.lastname: Bieniasz
authors.affiliation: Department of Integrative Physiology & Neuroscience, Washington State University, Pullman, WA 99614-7620, USA.
authors.forename: Janelle M
authors.initials: JM
authors.lastname: Lugo
authors.affiliation: Translational Addiction Research Center, Washington State University, Pullman, WA 99614-7620, USA; Department of Integrative Physiology & Neuroscience, Washington State University, Pullman, WA 99614-7620, USA; Department of Psychology, Washington State University, Pullman, WA 99614-7620, USA. Electronic address: ryanmclaughlin@vetmed.wsu.edu.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: McLaughlin
mesh_terms: D000818:Animals; D066272:Basolateral Nuclear Complex / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000378:metabolism*; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D009714:Nucleus Accumbens / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012201:Reward; D012727:Sex Characteristics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D017557:Ventral Tegmental Area / Q000378:metabolism
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol
keywords: alcohol; cytokine; mesocorticolimbic circuit; rat; sex differences; vapor