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

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

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. We tested the acute and lasting effects of c...

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Bibliographic Details
Published in:Biological psychiatry (1969) Vol. 95; no. 3; pp. 207 - 219
Main Authors: Secci, Maria E, Kelley, Leslie K, Avegno, Elizabeth M, Holmgren, Eleanor B, Chen, Lily, Rein, Sydney L, Engi, Sheila A, Quinlan, Virginia, Wilson, Lisa, Gilpin, Nicholas W, Wills, Tiffany A
Format: Journal Article
Language:English
Published: United States 01-02-2024
Subjects:
Adolescent
Animals
Central Amygdaloid Nucleus
Ethanol - pharmacology
Female
Humans
Hyperalgesia
Male
Pain
Rats
Underage Drinking
Rats
Ventral lateral periaqueductal gray
Alcohol
Central amygdala
Pain
Adolescents
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Summary: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. 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. 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. 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.
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ISSN:0006-3223
1873-2402
DOI:10.1016/j.biopsych.2023.09.006