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IL-1β expression is increased and regulates GABA transmission following chronic ethanol in mouse central amygdala.
Brain Behav Immun. 2019 01; 75:208-219.BB

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.

Authors+Show Affiliations

The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, USA.The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, USA.The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, USA.The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, USA.The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, USA.The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, USA.The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, USA.The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, USA.The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, USA.The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, USA.The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, USA.The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, USA. Electronic address: mroberto@scripps.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30791967

Citation

Patel, Reesha R., et al. "IL-1β Expression Is Increased and Regulates GABA Transmission Following Chronic Ethanol in Mouse Central Amygdala." Brain, Behavior, and Immunity, vol. 75, 2019, pp. 208-219.
Patel RR, Khom S, Steinman MQ, et al. IL-1β expression is increased and regulates GABA transmission following chronic ethanol in mouse central amygdala. Brain Behav Immun. 2019;75:208-219.
Patel, R. R., Khom, S., Steinman, M. Q., Varodayan, F. P., Kiosses, W. B., Hedges, D. M., Vlkolinsky, R., Nadav, T., Polis, I., Bajo, M., Roberts, A. J., & Roberto, M. (2019). IL-1β expression is increased and regulates GABA transmission following chronic ethanol in mouse central amygdala. Brain, Behavior, and Immunity, 75, 208-219. https://doi.org/10.1016/j.bbi.2018.10.009
Patel RR, et al. IL-1β Expression Is Increased and Regulates GABA Transmission Following Chronic Ethanol in Mouse Central Amygdala. Brain Behav Immun. 2019;75:208-219. PubMed PMID: 30791967.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - IL-1β expression is increased and regulates GABA transmission following chronic ethanol in mouse central amygdala. AU - Patel,Reesha R, AU - Khom,Sophia, AU - Steinman,Michael Q, AU - Varodayan,Florence P, AU - Kiosses,William B, AU - Hedges,David M, AU - Vlkolinsky,Roman, AU - Nadav,Tali, AU - Polis,Ilham, AU - Bajo,Michal, AU - Roberts,Amanda J, AU - Roberto,Marisa, Y1 - 2018/10/26/ PY - 2018/07/06/received PY - 2018/10/09/revised PY - 2018/10/25/accepted PY - 2019/2/23/entrez PY - 2019/2/23/pubmed PY - 2020/1/24/medline KW - Alcohol KW - CeA KW - Ethanol dependence KW - GABA KW - IL-1β SP - 208 EP - 219 JF - Brain, behavior, and immunity JO - Brain Behav Immun VL - 75 N2 - 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. SN - 1090-2139 UR - https://www.unboundmedicine.com/medline/citation/30791967/IL_1β_expression_is_increased_and_regulates_GABA_transmission_following_chronic_ethanol_in_mouse_central_amygdala_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0889-1591(18)30312-X DB - PRIME DP - Unbound Medicine ER -