Moderate Prenatal Alcohol Exposure Alters GABAergic Transmission and the Actions of Acute Alcohol in the Medial Central Amygdala of Adolescent Rats

Overview

Journal Neuropharmacology

Specialties Neurology
Pharmacology

Date 2024 Dec 26

PMID 39725126

Authors

Sarah E Winchester

Marvin R Diaz

Affiliations

Soon will be listed here.

Abstract

Individuals with prenatal alcohol exposure (PAE) are at a higher risk for developing alcohol use disorder (AUD). Using a rat model of moderate PAE (mPAE) 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 mPAE alters acute alcohol's effects within the CeM is unknown. Given these findings, we investigated how mPAE 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, mPAE 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 the middle concentration (66 mM), while mPAE males showed increased sIPSCs only at the highest tested concentration (88 mM). Adolescent females, regardless of PAE status, were largely insensitive to EtOH's effects at all tested concentrations. However, mPAE females showed a significant increase in sIPSCs at the highest tested concentration (88 mM). Overall, these findings support the hypothesis that mPAE leads to sex-specific changes in synaptic activity and neuronal function. Future research is needed to better understand the specific mechanisms by which acute EtOH affects neurotransmission in the adolescent brain of individuals with a history of PAE.

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