
Biological Psychiatry, Journal Year: 2025, Volume and Issue: unknown
Published: April 1, 2025
Alcohol use disorder (AUD) is a chronic relapsing and leading preventable cause of death worldwide. The central nucleus the amygdala (CeA) hub for stress AUD. Noradrenaline (norepinephrine; NE) regulates brain's response to alcohol. We previously reported that α1 adrenergic receptors drive moderate alcohol intake, while β contribute excessive drinking associated with dependence in male rats. Here, we determined withdrawal alter CeA noradrenergic system female rats using ex vivo electrophysiology, situ hybridization, site-specific behavioral pharmacology, RNA-sequencing data from postmortem samples obtained donors without NE bidirectionally (increase decrease) modulated GABAergic transmission via both receptors. Prazosin, an receptor antagonist, reduced intake non-dependent dependent females, propranolol, only females. While produced partial functional recovery modulation CeA, some cellular patterns mRNA expression persist. Although did not observe any differences gene our human AUD donors, found downregulation ADRA1A basolateral dorsolateral prefrontal cortex, compared controls. Amygdalar are key neural substrates Our results support ongoing development receptor-specific medication highlight promising efficacy
Language: Английский