Age- and cytokine-dependent modulation of GABAergic transmission within the basolateral amygdala of male Sprague Dawley rats

Alcohol binge drinking has a multitude of effects on CNS function, including changes in inflammatory cytokines such as IL-6 and IL-1β that may contribute to mood fluctuations associated with the intoxication-withdrawal cycle. Widely throughout the brain, including the amygdala, IL-6 mRNA is enhanced during intoxication, whereas IL-1β is initially suppressed during alcohol intoxication, with increased expression seen shortly after ethanol clearance, during acute hangover. Furthermore, induction of neuroimmune genes appears to be muted during adolescence in the amygdala, suggesting a broader functional immaturity of the adolescent neuroimmune system in structures involved in negative affect associated with ethanol exposure. However, neither the effect of IL-6 or IL-1β on synaptic function within the amygdala nor the impact of acute intoxication and withdrawal on these cytokines' function are known. To test this, we used whole-cell patch-clamp electrophysiology to assess the effects of IL-6 and IL-1β on GABA-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) in BLA pyramidal neurons from male rats in early adolescence (P28-40) or adulthood (P70+). These experiments were done in naïve, intoxicated (3-4 hours following an intraperitoneal injection of 3.5 g/kg ethanol), and during acute hangover (11-18 hours post ethanol injection). In naïve males, we found that IL-6 (10 ng/ml) significantly enhanced sIPSC amplitude only in adults, with no apparent effect in adolescents; this effect of IL-6 in adults was not different during intoxication. Conversely, IL-1β (10 ng/ml) did not alter sIPSC frequency in any group (naïve or withdrawal adolescents or adults). Unlike our previous work in adult rats, here we found that contextual fear conditioning was not altered in adolescents when conditioned during acute hangover. Together, these observations suggest that IL-6, but not IL-1β, regulation of BLA GABA transmission emerges as a function of age, but is not affected by intoxication or withdrawal for adolescents or adults. Importantly, these findings provide additional evidence to support functional immaturity of the neuroimmune system in adolescence.