Moderate prenatal alcohol exposure alters GABAergic transmission and the action of acute alcohol in the CeM of adolescent rats

Individuals with prenatal alcohol exposure (PAE) are at a higher risk for developing alcohol use disorder (AUD). Using a rat model of PAE on gestational day 12 (G12; ~2nd trimesters in humans), a critical period for amygdala development, we have shown disruptions in medial central amygdala (CeM) function, an important brain region associated with the development of AUD. In addition to this, acute ethanol (EtOH) increases GABA transmission in the CeM of rodents in a sex-dependent manner, a mechanism that potentially contributes to alcohol misuse. How PAE alters acute alcohols effects within the CeM is unknown. Given these findings, we investigated how PAE may interact with acute alcohol to alter neuronal and synaptic mechanisms in the CeM of adolescent rats in order to understand PAE-induced alcohol-related behaviors. Under basal conditions, PAE males showed reduced rheobase, indicative of reduced excitability, and females showed a reduction in GABA transmission, indicated by lower spontaneous inhibitory postsynaptic currents (sIPSCs). We found that acute EtOH increased sIPSCs in control males at a moderate concentration (66 mM), while PAE males showed increased sIPSCs only at a high concentration (88 mM). Adolescent females, regardless of PAE status, were largely insensitive to EtOHs effects at all tested concentrations. However, PAE females showed a significant increase in sIPSCs at the highest concentration (88 mM). Overall, these findings support the hypothesis that PAE leads to sex-specific changes in synaptic activity and neuronal function. Future research is needed to better understand the specific mechanisms by which acute EtOHs affects neurotransmission in the adolescent brain of individuals with a history of PAE.