Conditioned effects of ethanol on the neuroimmune system

ANNY GANO; PAUTASSI R.M.; TAMARA DOREMUS-FITZWATER; TERRENCE DEAK

EXPERIMENTAL BIOLOGY AND MEDICINE

SOC EXPERIMENTAL BIOLOGY MEDICINE

Lugar: Maywood; Año: 2017 vol. 242 p. 718 - 730

1535-3702

Several studies indicate that the immune system can be subjected to classical conditioning.Acute ethanol intoxication significantly modulates several pro-inflammatory cytokines (e.g.interleukins-1 and 6 [IL-1b and IL-6, respectively] and tumor necrosis factor alpha [TNFa])) inseveral brain areas, including amygdala (AMG), paraventricular nucleus (PVN), and hippocampus(HPC). It is unknown, however, whether cues associated with ethanol can elicitconditioned alterations in cytokine expression. The present study analyzed, in maleSprague-Dawley rats, whether ethanol-induced changes in the central cytokine responsemay be amenable to conditioning. In Experiments 1 and 2, the rats were given one or twopairings between a distinctive odor (conditional stimulus, CS) and the post-absorptiveeffects of a high (3.0 or 4.0 g/kg, Experiments 1 and 2, respectively) ethanol dose. Neitherof these experiments revealed conditioning of IL-6, IL-1b, or TNFa, as measured via mRNAlevels. Yet, re-exposure to the lemon-odor CS in Experiment 1 significantly increased C-Foslevels in the PVN. In Experiment 3, the rats were given four pairings between an odor CS anda moderate ethanol dose (2.0 g/kg), delivered intraperitoneally (i.p.) or intragastrically (i.g.).Re-exposure to the odor CS significantly increased IL-6 levels in HPC and AMG, an effectonly evident in paired rats administered ethanol i.p. Overall, this study suggests that ethanolexposure can regulate the levels of IL-6 at HPC and AMG via classical conditioning mechanisms.These ethanol-induced, conditioned alterations in cytokine levels may ultimatelyaffect the intake and motivational effects of ethanol.