Synaptic effects of IL-1β and CRF in the central amygdala after protracted alcohol abstinence in male rhesus macaques

Reesha R. Patel, Florence P. Varodayan, Melissa A. Herman, Vanessa Jimenez, Rebecca Agnore, Lina Gao, Michal Bajo, Verginia C. Cuzon Carlson, Nicole A. Walter, Suzanne S. Fei, Kathleen (Kathy) Grant, Marisa Roberto

    Research output: Contribution to journalArticlepeer-review

    Abstract

    A major barrier to remission from an alcohol use disorder (AUD) is the continued risk of relapse during abstinence. Assessing the neuroadaptations after chronic alcohol and repeated abstinence is important to identify mechanisms that may contribute to relapse. In this study, we used a rhesus macaque model of long-term alcohol use and repeated abstinence, providing a platform to extend mechanistic findings from rodents to primates. The central amygdala (CeA) displays elevated GABA release following chronic alcohol in rodents and in abstinent male macaques, highlighting this neuroadaptation as a conserved mechanism that may underlie excessive alcohol consumption. Here, we determined circulating interleukin-1β (IL-1β) levels, CeA transcriptomic changes, and the effects of IL-1β and corticotropin releasing factor (CRF) signaling on CeA GABA transmission in male controls and abstinent drinkers. While no significant differences in peripheral IL-1β or the CeA transcriptome were observed, pathway analysis identified several canonical immune-related pathways. We addressed this potential dysregulation of CeA immune signaling in abstient drinkers with an electrophysiological approach. We found that IL-1β decreased CeA GABA release in controls while abstinent drinkers were less sensitive to IL-1β’s effects, suggesting adaptations in the neuromodulatory role of IL-1β. In contrast, CRF enhanced CeA GABA release similarly in controls and abstinent drinkers, consistent with rodent studies. Notably, CeA CRF expression was inversely correlated with intoxication, suggesting that CRF levels during abstinence may predict future intoxication. Together, our findings highlight conserved and divergent actions of chronic alcohol on neuroimmune and stress signaling on CeA GABA transmission across rodents and macaques.

    Original languageEnglish (US)
    JournalNeuropsychopharmacology
    DOIs
    StateAccepted/In press - 2021

    ASJC Scopus subject areas

    • Pharmacology
    • Psychiatry and Mental health

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