Adolescent Alcohol Exposure Produces Sex-Specific Long-term Hyperalgesia Via Changes in Central Amygdala Circuit Function

Overview

Journal Biol Psychiatry

Publisher Elsevier

Specialty Psychiatry

Date 2023 Sep 17

PMID 37717844

Authors

Maria E Secci

Leslie K Kelley

Elizabeth M Avegno

Eleanor B Holmgren

Lily Chen

Sydney L Rein

Sheila A Engi

Virginia Quinlan

Lisa Wilson

Nicholas W Gilpin

Tiffany A Wills

Affiliations

Soon will be listed here.

Abstract

Background: Exposure to alcohol during adolescence produces many effects that last well into adulthood. Acute alcohol use is analgesic, and people living with pain report drinking alcohol to reduce pain, but chronic alcohol use produces increases in pain sensitivity.

Methods: We tested the acute and lasting effects of chronic adolescent intermittent ethanol (AIE) exposure on pain-related behavioral and brain changes in male and female rats. We also tested the long-term effects of AIE on synaptic transmission in midbrain (ventrolateral periaqueductal gray [vlPAG])-projecting central amygdala (CeA) neurons using whole-cell electrophysiology. Finally, we used circuit-based approaches (DREADDs [designer receptors exclusively activated by designer drugs]) to test the role of vlPAG-projecting CeA neurons in mediating AIE effects on pain-related outcomes.

Results: AIE produced long-lasting hyperalgesia in male, but not female, rats. Similarly, AIE led to a reduction in synaptic strength of medial CeA cells that project to the vlPAG in male, but not female, rats. Challenge with an acute painful stimulus (i.e., formalin) in adulthood produced expected increases in pain reactivity, and this effect was exaggerated in male rats with a history of AIE. Finally, CeA-vlPAG circuit activation rescued AIE-induced hypersensitivity in male rats.

Conclusions: Our findings are the first, to our knowledge, to show long-lasting sex-dependent effects of adolescent alcohol exposure on pain-related behaviors and brain circuits in adult animals. This work has implications for understanding the long-term effects of underage alcohol drinking on pain-related behaviors in humans.

Citing Articles

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