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bioRxiv · 10.64898/2025.12.12.693987

Moderate prenatal alcohol exposure differentially alters acute ethanol sensitivity of GABAergic transmission in CRFR1- and CRFR1+ CeM neurons

Winchester, S.·Diaz, M. R.
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Abstract

AbstractPrenatal exposure to alcohol (PAE) increases the risk for misusing alcohol and/or developing an alcohol use disorder (AUD) by adulthood. The corticotropin releasing factor (CRF) system is a major target of pre- and post-natal ethanol (EtOH) exposure. CRF and its receptor (CRFR1), in part, mediate EtOH potentiated GABA release in the medial nucleus of the central amygdala (CeM) of adult male rodents. Interestingly, our lab has shown a disruption in the function and expression of CeM CRFR1 and acute EtOHs effects on GABA transmission in PAE adolescent animals, but it is unknown whether these alterations to the CRF system persist into adulthood or alter the actions of acute EtOH on GABAergic transmission in the CeM. Using CRF1-Cre-tdTomato rats, this study examined how moderate PAE alters acute EtOH modulation of GABAergic neurotransmission onto CRFR1+ and CRFR1-CeM neurons in adult offspring (P80-105). Pregnant dams were exposed to vaporized ethanol or room air (control) on gestational day 12 (G12) for 6 hours and whole-cell electrophysiology was performed in the CeM to assess the actions of acute EtOH (44, 66, & 88 mM) on GABAergic transmission onto CRFR1+ and CRFR1-neurons. We found unique effects of PAE that were cell type- and concentration-dependent in males and females, suggesting PAE dysregulates acute EtOHs modulation of GABA transmission within the CeM in a sex-specific manner. This study contributes to the expanding body of research exploring the effects of PAE and how a single exposure can impact neurophysiological mechanisms in brain regions associated with AUD. HighlightsO_LIModerate PAE alters the actions of alcohol on synaptic transmission in adult rats C_LIO_LIPAE differentially impacts GABAergic transmission onto CeM CRFR1- and CRFR1+ C_LIO_LILong-term PAE effects in the CeM are sex-specific C_LI

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Winchester, S., Diaz, M. R.. 2025-12-16. Moderate prenatal alcohol exposure differentially alters acute ethanol sensitivity of GABAergic transmission in CRFR1- and CRFR1+ CeM neurons. https://doi.org/10.64898/2025.12.12.693987

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