Assessment of Interleukin-6 Signaling Effects on Behavioral Changes Associated with Acute Alcohol Intoxication in adult male rats.

Recent studies have demonstrated unique brain cytokine signatures associated with acute ethanol intoxication (increased IL-6) and withdrawal (increased IL-1β and TNFα). The purpose of the present studies was to examine the potential functional role of increased central interleukin-6 (IL-6). We utilized two tests of ethanol sensitivity to establish a potential role for IL-6 after high (3.5-4.0 g/kg i.p) or moderate (2.0 g/kg i.p) doses of ethanol: loss of righting reflex (LORR) and conditioned taste aversion (CTA), respectively. Briefly, guide cannula were implanted into the third ventricle of adult male Sprague-Dawley rats. In the first experiments, rats were infused with: 25, 50, 100, or 200 ng of IL-6; or 0.3, 3.0, or 9.0 μg of the JAK/STAT inhibitor AG490 30 min prior to a high dose ethanol challenge. Although sleep time was not affected by exogenous IL-6, infusion of AG490 increased latency to lose the righting reflex relative to vehicle infused rats. Next, we assessed whether IL-6 was sufficient to produce a CTA. Moderately water-deprived rats received i.c.v. infusions of 25, 50, or 100 ng IL-6 immediately after 60 min access to 5% sucrose solution. 48 hr later, rats were returned to the context and given 60 min access to sucrose solution. IL-6 infusion had no significant effect on sucrose intake when all rats were considered together. However, a median split revealed that low sucrose-consuming rats significantly increased their drinking on test day, an effect that was not seen in rats that received 50 or 100 ng of IL-6. In the last study, AG490 had no effect on ethanol-induced CTA (2 g/kg). Overall, these studies suggest that IL-6 had only a minor influence on ethanol-induced behavioral changes, yet phenotypic differences in sensitivity to IL-6 were apparent. These studies are among the first to examine a potential functional role for IL-6 in ethanol-related behaviors, and may have important implications for understanding the relationship between acute ethanol intoxication and its associated behavioral alterations.