Alcohol-induced neuroimmune and hormonal conditioning following a conditioned taste aversion procedure

ANNY GANO; BARNEY, R.M.; PAUTASSI R.M.; TERRENCE DEAK

Washington

Congreso; 2017 Society for Neuroscience Meeting; 2017

Society for Neuroscience (SFN)

Ethanol-induced conditioning of the neuroimmune and corticosterone response following a conditioned taste aversion procedure.A.Gano, T. Barney, R. M. Pautassi, T. Deak.Prior work from our lab has shown expression of several inflammation-related genes in the CNS [including both Interleukin (IL)-6 and IκBα (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha)] after acute, binge-like ethanol exposure. More recently, repeated pairings of external cues (odorized context) and subthreshold (2 g/kg intraperitoneal [i.p.]; does not induce IL-6) ethanol administration produced context-dependent sensitization of IL-6 in the hippocampus (Gano et al., 2017), suggesting that central cytokine response to ethanol can come under environmental control. The present studies tested the emergence of conditioned increases in IL-6 after a conditioned taste aversion (CTA) procedure. In Experiment 1, adolescent (P32) and adult (P75) Sprague-Dawley rats were exposed to a novel, lavender-scented context for 3.5 h, with access to 5% sucrose for the first 30 min of exposure. Rats received 4 g/kg i.p. ethanol immediately after termination of the sucrose access period. An explicitly unpaired control group received the same volume ethanol injection separately from context exposure. Both ages displayed a significant, ethanol-induced CTA. Adolescents, but not adults, displayed a significant, conditioned IL-6 elevation in the nucleus of the tractus solitarius (NTS). This indicated an age-related difference in sensitivity to ethanol-induced neuroimmune conditioning. Experiment 2 recreated the conditioning procedure of Experiment 1 in P40 adolescent females using a wider range of ethanol doses (1.0, 2.0, or 4.0 g/kg i.p.), as well as control groups receiving a paired saline injection equivolumetric to the high ethanol dose (0.0 g/kg), or 4 g/kg i.p. ethanol separate from context exposure. Sucrose consumption data revealed dose-dependent CTA. Despite the fact that neuroimmune conditioned responses were not observed, rats trained with 2.0 g/kg displayed a significant, conditioned increase in plasma corticosterone. These data confirm and extend our previous findings showing that ethanol-related cytokine induction in the CNS can be conditioned to previously neutral cues associated with drug exposure, and that these effects are dependent on the specific conditioning paradigm, age, and brain region. Future work will be necessary to discern the contribution of conditioned immune and hormone activity to established sex differences in ethanol-related learning, development of alcohol addiction, and relapse. Supported by the Developmental Exposure Alcohol Research Center (P50AA017823)