IL-1β expression is increased and regulates GABA transmission following chronic ethanol in mouse central amygdala

Reesha R. Patel, Sophia Khom, Michael Q. Steinman, Florence P. Varodayan, William B. Kiosses, David M. Hedges, Roman Vlkolinsky, Tali Nadav, Ilham Polis, Michal Bajo, Amanda J. Roberts, Marisa Roberto*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

The interleukin-1 system (IL-1) is a prominent pro-inflammatory pathway responsible for the initiation and regulation of immune responses. Human genetic and preclinical studies suggest a critical role for IL-1β signaling in ethanol drinking and dependence, but little is known about the effects of chronic ethanol on the IL-1 system in addiction-related brain regions such as the central amygdala (CeA). In this study, we generated naïve, non-dependent (Non-Dep) and dependent (Dep) male mice using a paradigm of chronic-intermittent ethanol vapor exposure interspersed with two-bottle choice to examine 1) the expression of IL-1β, 2) the role of the IL-1 system on GABAergic transmission, and 3) the potential interaction with the acute effects of ethanol in the CeA. Immunohistochemistry with confocal microscopy was used to assess expression of IL-1β in microglia and neurons in the CeA, and whole-cell patch clamp recordings were obtained from CeA neurons to measure the effects of IL-1β (50 ng/ml) or the endogenous IL-1 receptor antagonist (IL-1ra; 100 ng/ml) on action potential-dependent spontaneous inhibitory postsynaptic currents (sIPSCs). Overall, we found that IL-1β expression is significantly increased in microglia and neurons of Dep compared to Non-Dep and naïve mice, IL-1β and IL-1ra bi-directionally modulate GABA transmission through both pre- and postsynaptic mechanisms in all three groups, and IL-1β and IL-1ra do not alter the facilitation of GABA release induced by acute ethanol. These data suggest that while ethanol dependence induces a neuroimmune response in the CeA, as indicated by increased IL-1β expression, this does not significantly alter the neuromodulatory role of IL-1β on synaptic transmission.

Original languageEnglish (US)
Pages (from-to)208-219
Number of pages12
JournalBrain, Behavior, and Immunity
Volume75
DOIs
StatePublished - Jan 2019

Keywords

  • Alcohol
  • CeA
  • Ethanol dependence
  • GABA
  • IL-1β

ASJC Scopus subject areas

  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience
  • Immunology

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