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Here, we used our established rat model of comorbid post-traumatic stress disorder (PTSD)\/AUD to characterize the interleukin 18 (IL-18) system in the central amygdala (CeA). Male and female rats underwent novel (NOV) and familiar (FAM) shock stress, or no stress (unstressed controls; CTL) followed by voluntary alcohol drinking and PTSD-related behaviors, then all received renewed alcohol access prior to the experiments. In situ hybridization revealed that the number of CeA positive cells for Il18 mRNA increased, while for Il18bp decreased in both male and female FAM stressed rats versus CTL. No changes were observed in Il18r1 expression across groups. Ex vivo electrophysiology showed that IL-18 reduced GABAA-mediated miniature inhibitory postsynaptic currents (mIPSCs) frequencies in CTL, suggesting reduced CeA GABA release, regardless of sex. Notably, this presynaptic effect of IL-18 was lost in both NOV and FAM males, while it persisted in NOV and FAM females. IL-18 decreased mIPSC amplitude in CTL female rats, suggesting postsynaptic effects. Overall, our results suggest that stress in rats with alcohol access impacts CeA IL-18-system expression and, in sex-related fashion, IL-18\u2032s modulatory function at GABA synapses.<\/jats:p>","DOI":"10.3390\/cells12151943","type":"journal-article","created":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T01:50:37Z","timestamp":1690422637000},"page":"1943","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["IL-18 Signaling in the Rat Central Amygdala Is Disrupted in a Comorbid Model of Post-Traumatic Stress and Alcohol Use Disorder"],"prefix":"10.3390","volume":"12","author":[{"given":"Vittoria","family":"Borgonetti","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92073, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7418-1524","authenticated-orcid":false,"given":"Bryan","family":"Cruz","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92073, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6868-3424","authenticated-orcid":false,"given":"Valentina","family":"Vozella","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92073, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"Khom","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92073, USA"},{"name":"Department of Pharmaceutical Sciences, University of Vienna, Josef-Holaubek-Platz 2, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael Q.","family":"Steinman","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92073, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Bullard","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92073, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon","family":"D\u2019Ambrosio","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92073, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher S.","family":"Oleata","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92073, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Vlkolinsky","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92073, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Bajo","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92073, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric P.","family":"Zorrilla","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92073, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean","family":"Kirson","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92073, USA"},{"name":"Department of Pharmacology, Addiction Science, and Toxicology, The University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0729-3961","authenticated-orcid":false,"given":"Marisa","family":"Roberto","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92073, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"72","DOI":"10.3389\/fpsyt.2013.00072","article-title":"Addiction is a Reward Deficit and Stress Surfeit Disorder","volume":"4","author":"Koob","year":"2013","journal-title":"Front. Psychiatry"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1196\/annals.1441.030","article-title":"Chronic stress, drug use, and vulnerability to addiction","volume":"1141","author":"Sinha","year":"2008","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1111\/j.1369-1600.2012.00460.x","article-title":"Stress history increases alcohol intake in relapse: Relation to phosphodiesterase 10A","volume":"17","author":"Logrip","year":"2012","journal-title":"Addict. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.neuropharm.2011.07.007","article-title":"Stress modulation of drug self-administration: Implications for addiction comorbidity with post-traumatic stress disorder","volume":"62","author":"Logrip","year":"2012","journal-title":"Neuropharmacology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1111\/j.1360-0443.1991.tb03098.x","article-title":"Increased severity of alcohol withdrawal in in-patient alcoholics with a co-existing anxiety diagnosis","volume":"86","author":"Johnston","year":"1991","journal-title":"Br. J. Addict."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.eurpsy.2013.08.006","article-title":"Co-morbid anxiety disorders predict early relapse after inpatient alcohol treatment","volume":"30","author":"Schellekens","year":"2015","journal-title":"Eur. Psychiatry J. Assoc. Eur. Psychiatr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s00213-011-2443-9","article-title":"Effects of stress on alcohol drinking: A review of animal studies","volume":"218","author":"Becker","year":"2011","journal-title":"Psychopharmacology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/gbb.12349","article-title":"Neurobiology of comorbid post-traumatic stress disorder and alcohol-use disorder","volume":"16","author":"Gilpin","year":"2017","journal-title":"Genes Brain Behav."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.pbb.2003.07.001","article-title":"High-alcohol-drinking rats exhibit persistent freezing responses to discrete cues following Pavlovian fear conditioning","volume":"76","author":"Rorick","year":"2003","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1007\/s00213-002-1267-z","article-title":"Stimulus conditioned to foot-shock stress reinstates alcohol-seeking behavior in an animal model of relapse","volume":"168","author":"Liu","year":"2003","journal-title":"Psychopharmacology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1111\/acer.12012","article-title":"Stress increases voluntary alcohol intake, but does not alter established drinking habits in a rat model of posttraumatic stress disorder","volume":"37","author":"Meyer","year":"2013","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3093","DOI":"10.1038\/s41380-020-00920-2","article-title":"Importance of sex and trauma context on circulating cytokines and amygdalar GABAergic signaling in a comorbid model of posttraumatic stress and alcohol use disorders","volume":"26","author":"Steinman","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1038\/s41386-022-01497-w","article-title":"FKBP5 inhibitors modulate alcohol drinking and trauma-related behaviors in a model of comorbid post-traumatic stress and alcohol use disorder","volume":"48","author":"Cruz","year":"2023","journal-title":"Neuropsychopharmacology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1037\/0033-295X.108.1.4","article-title":"A modern learning theory perspective on the etiology of panic disorder","volume":"108","author":"Bouton","year":"2001","journal-title":"Psychol. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1101\/lm.70204","article-title":"The role of muscarinic and nicotinic cholinergic neurotransmission in aversive conditioning: Comparing pavlovian fear conditioning and inhibitory avoidance","volume":"11","author":"Tinsley","year":"2004","journal-title":"Learn. Mem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.conb.2013.01.024","article-title":"Neuroimmune signaling: A key component of alcohol abuse","volume":"23","author":"Mayfield","year":"2013","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1111\/j.1530-0277.2006.00084.x","article-title":"Cytokines and alcohol","volume":"30","author":"Crews","year":"2006","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.alcohol.2007.03.003","article-title":"Functional gene expression differences between inbred alcohol-preferring and -non-preferring rats in five brain regions","volume":"41","author":"Kimpel","year":"2007","journal-title":"Alcohol"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1523\/JNEUROSCI.3136-11.2012","article-title":"Gene co-expression networks in human brain identify epigenetic modifications in alcohol dependence","volume":"32","author":"Ponomarev","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6368","DOI":"10.1073\/pnas.0510188103","article-title":"Toward understanding the genetics of alcohol drinking through transcriptome meta-analysis","volume":"103","author":"Mulligan","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.expneurol.2007.11.017","article-title":"Increased MCP-1 and microglia in various regions of the human alcoholic brain","volume":"210","author":"He","year":"2008","journal-title":"Exp. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1016\/j.biopsych.2020.05.011","article-title":"Microglia control escalation of drinking in alcohol dependent mice: Genomic and synaptic drivers","volume":"88","author":"Warden","year":"2020","journal-title":"Biol. Psychiatry"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.nbd.2008.04.009","article-title":"Distinct cell proliferation events during abstinence after alcohol dependence: Microglia proliferation precedes neurogenesis","volume":"31","author":"Nixon","year":"2008","journal-title":"Neurobiol. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"289","DOI":"10.3389\/fimmu.2013.00289","article-title":"Interleukin-18 and IL-18 binding protein","volume":"4","author":"Dinarello","year":"2013","journal-title":"Front. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/1742-2094-7-9","article-title":"Interleukin 18 in the CNS","volume":"7","author":"Alboni","year":"2010","journal-title":"J. Neuroinflammation"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.brainresrev.2007.11.003","article-title":"Interleukin-18 and stress","volume":"58","author":"Sugama","year":"2008","journal-title":"Brain Res. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5347","DOI":"10.1007\/s12035-016-0052-7","article-title":"Local Interleukin-18 System in the Basolateral Amygdala Regulates Susceptibility to Chronic Stress","volume":"54","author":"Kim","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5359","DOI":"10.1007\/s12035-016-0139-1","article-title":"Erratum to: Local Interleukin-18 System in the Basolateral Amygdala Regulates Susceptibility to Chronic Stress","volume":"54","author":"Kim","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.jneuroim.2017.11.008","article-title":"Mice lacking interleukin-18 gene display behavioral changes in animal models of psychiatric disorders: Possible involvement of immunological mechanisms","volume":"314","author":"Lisboa","year":"2018","journal-title":"J. Neuroimmunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/S1074-7613(00)80013-8","article-title":"Interleukin-18 binding protein: A novel modulator of the Th1 cytokine response","volume":"10","author":"Novick","year":"1999","journal-title":"Immunity"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/S0014-5793(99)00148-9","article-title":"Cloning and expression of interleukin-18 binding protein","volume":"445","author":"Aizawa","year":"1999","journal-title":"FEBS Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.neuropharm.2015.03.015","article-title":"Role of interleukin-1 receptor signaling in the behavioral effects of ethanol and benzodiazepines","volume":"95","author":"Blednov","year":"2015","journal-title":"Neuropharmacology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4733","DOI":"10.4049\/jimmunol.0803590","article-title":"Critical role of TLR4 response in the activation of microglia induced by ethanol","volume":"183","author":"Pascual","year":"2009","journal-title":"J. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.neuropharm.2014.10.014","article-title":"Cytokines and chemokines as biomarkers of ethanol-induced neuroinflammation and anxiety-related behavior: Role of TLR4 and TLR2","volume":"89","author":"Pascual","year":"2015","journal-title":"Neuropharmacology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.bbr.2014.10.053","article-title":"Traumatic brain injury induces neuroinflammation and neuronal degeneration that is associated with escalated alcohol self-administration in rats","volume":"279","author":"Mayeux","year":"2015","journal-title":"Behav. Brain Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.bbi.2023.02.020","article-title":"Chronic ethanol induces a pro-inflammatory switch in interleukin-1beta regulation of GABAergic signaling in the medial prefrontal cortex of male mice","volume":"110","author":"Varodayan","year":"2023","journal-title":"Brain Behav. Immun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.bbi.2018.10.009","article-title":"IL-1beta expression is increased and regulates GABA transmission following chronic ethanol in mouse central amygdala","volume":"75","author":"Patel","year":"2019","journal-title":"Brain Behav. Immun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1002\/jlb.63.6.658","article-title":"Overview of interleukin-18: More than an interferon-gamma inducing factor","volume":"63","author":"Dinarello","year":"1998","journal-title":"J. Leukoc. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1172\/JCI7317","article-title":"A proinflammatory role for IL-18 in rheumatoid arthritis","volume":"104","author":"Gracie","year":"1999","journal-title":"J. Clin. Investig."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1016\/j.biopsych.2010.10.014","article-title":"Association of plasma interleukin-18 levels with emotion regulation and mu-opioid neurotransmitter function in major depression and healthy volunteers","volume":"69","author":"Prossin","year":"2011","journal-title":"Biol. Psychiatry"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.smim.2013.10.014","article-title":"Interleukin-18, more than a Th1 cytokine","volume":"25","author":"Novick","year":"2013","journal-title":"Semin. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1159\/000354764","article-title":"Increased levels of serum IL-18 are associated with the long-term outcome of severe traumatic brain injury","volume":"21","author":"Ciaramella","year":"2014","journal-title":"Neuroimmunomodulation"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.imlet.2004.12.003","article-title":"Regulation of IL-18 expression by CRH in mouse microglial cells","volume":"98","author":"Yang","year":"2005","journal-title":"Immunol. Lett."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s12974-018-1054-3","article-title":"Microglial activation mediates chronic mild stress-induced depressive- and anxiety-like behavior in adult rats","volume":"15","author":"Wang","year":"2018","journal-title":"J. Neuroinflammation"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.4103\/1673-5374.276358","article-title":"Interleukin-18 levels in the hippocampus and behavior of adult rat offspring exposed to prenatal restraint stress during early and late pregnancy","volume":"15","author":"Chen","year":"2020","journal-title":"Neural Regen. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/j.biopsych.2014.09.008","article-title":"The central amygdala as an integrative hub for anxiety and alcohol use disorders","volume":"77","author":"Gilpin","year":"2015","journal-title":"Biol. Psychiatry"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"a039339","DOI":"10.1101\/cshperspect.a039339","article-title":"The Role of the Central Amygdala in Alcohol Dependence","volume":"11","author":"Roberto","year":"2021","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1111\/j.1749-6632.1999.tb09273.x","article-title":"The extended amygdala: Are the central nucleus of the amygdala and the bed nucleus of the stria terminalis differentially involved in fear versus anxiety?","volume":"877","author":"Davis","year":"1999","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1038\/nature14188","article-title":"From circuits to behaviour in the amygdala","volume":"517","author":"Janak","year":"2015","journal-title":"Nature"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.neuroscience.2011.03.051","article-title":"Altered GABA transmission in a mouse model of increased trait anxiety","volume":"183","author":"Tasan","year":"2011","journal-title":"Neuroscience"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"105610","DOI":"10.1016\/j.nbd.2022.105610","article-title":"Alcohol dependence and withdrawal increase sensitivity of central amygdalar GABAergic synapses to the glucocorticoid receptor antagonist mifepristone in male rats","volume":"164","author":"Khom","year":"2022","journal-title":"Neurobiol. Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"eaaz1050","DOI":"10.1126\/sciadv.aaz1050","article-title":"Alcohol dependence potentiates substance P\/neurokinin-1 receptor signaling in the rat central nucleus of amygdala","volume":"6","author":"Khom","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"6842","DOI":"10.1523\/JNEUROSCI.0733-20.2020","article-title":"Alcohol Dependence and Withdrawal Impair Serotonergic Regulation of GABA Transmission in the Rat Central Nucleus of the Amygdala","volume":"40","author":"Khom","year":"2020","journal-title":"J. Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.biopsych.2009.11.007","article-title":"Corticotropin Releasing Factor-Induced Amygdala Gamma-Aminobutyric Acid Release Plays a Key Role in Alcohol Dependence","volume":"67","author":"Roberto","year":"2010","journal-title":"Biol. Psychiatry"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"10159","DOI":"10.1523\/JNEUROSCI.3004-04.2004","article-title":"Increased GABA release in the central amygdala of ethanol-dependent rats","volume":"24","author":"Roberto","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1073\/pnas.0437926100","article-title":"Ethanol increases GABAergic transmission at both pre- and postsynaptic sites in rat central amygdala neurons","volume":"100","author":"Roberto","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.neuropharm.2017.08.009","article-title":"CRF modulates glutamate transmission in the central amygdala of naive and ethanol-dependent rats","volume":"125","author":"Varodayan","year":"2017","journal-title":"Neuropharmacology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"10729","DOI":"10.1523\/JNEUROSCI.1267-16.2016","article-title":"A Functional Switch in Tonic GABA Currents Alters the Output of Central Amygdala Corticotropin Releasing Factor Receptor-1 Neurons Following Chronic Ethanol Exposure","volume":"36","author":"Herman","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"101952","DOI":"10.1016\/j.pneurobio.2020.101952","article-title":"IL-10 normalizes aberrant amygdala GABA transmission and reverses anxiety-like behavior and dependence-induced escalation of alcohol intake","volume":"199","author":"Patel","year":"2021","journal-title":"Prog. Neurobiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1038\/s41386-021-01231-y","article-title":"Synaptic effects of IL-1beta and CRF in the central amygdala after protracted alcohol abstinence in male rhesus macaques","volume":"47","author":"Patel","year":"2022","journal-title":"Neuropsychopharmacology"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1038\/s41386-018-0290-7","article-title":"Synaptic adaptations in the central amygdala and hypothalamic paraventricular nucleus associated with protracted ethanol abstinence in male rhesus monkeys","volume":"44","author":"Jimenez","year":"2019","journal-title":"Neuropsychopharmacology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1126\/science.aao1157","article-title":"A molecular mechanism for choosing alcohol over an alternative reward","volume":"360","author":"Augier","year":"2018","journal-title":"Science"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3354","DOI":"10.1002\/jnr.24972","article-title":"Sex and context differences in the effects of trauma on comorbid alcohol use and post-traumatic stress phenotypes in actively drinking rats","volume":"99","author":"Kirson","year":"2021","journal-title":"J. Neurosci. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/S0169-328X(00)00069-3","article-title":"Detection of the interleukin 18 family in rat brain by RT-PCR","volume":"77","author":"Wheeler","year":"2000","journal-title":"Brain Res. Mol. Brain Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.jneuroim.2009.06.016","article-title":"Mapping of the full length and the truncated interleukin-18 receptor alpha in the mouse brain","volume":"214","author":"Alboni","year":"2009","journal-title":"J. Neuroimmunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.bbi.2010.11.011","article-title":"Constitutive and LPS-regulated expression of interleukin-18 receptor beta variants in the mouse brain","volume":"25","author":"Alboni","year":"2011","journal-title":"Brain Behav. Immun."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.jneuroim.2010.07.024","article-title":"Interleukin-18 deficiency reduces neuropeptide gene expressions in the mouse amygdala related with behavioral change","volume":"229","author":"Yamamoto","year":"2010","journal-title":"J. Neuroimmunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"11097","DOI":"10.1073\/pnas.0611523104","article-title":"Interleukin-18 controls energy homeostasis by suppressing appetite and feed efficiency","volume":"104","author":"Zorrilla","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1001\/archgenpsychiatry.2011.50","article-title":"Using polymorphisms in FKBP5 to define biologically distinct subtypes of posttraumatic stress disorder: Evidence from endocrine and gene expression studies","volume":"68","author":"Mehta","year":"2011","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1111\/adb.12569","article-title":"Problematic alcohol use associates with sodium channel and clathrin linker 1 (SCLT1) in trauma-exposed populations","volume":"23","author":"Almli","year":"2018","journal-title":"Addict. Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1038\/npp.2016.129","article-title":"A Functional Interleukin-18 Haplotype Predicts Depression and Anxiety through Increased Threat-Related Amygdala Reactivity in Women but Not Men","volume":"42","author":"Swartz","year":"2017","journal-title":"Neuropsychopharmacology"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/mp.2017.77","article-title":"Largest GWAS of PTSD (N = 20070) yields genetic overlap with schizophrenia and sex differences in heritability","volume":"23","author":"Duncan","year":"2018","journal-title":"Mol. Psychiatry"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1523\/ENEURO.0087-19.2019","article-title":"Molecular, Morphological, and Functional Characterization of Corticotropin-Releasing Factor Receptor 1-Expressing Neurons in the Central Nucleus of the Amygdala","volume":"6","author":"Wolfe","year":"2019","journal-title":"eNeuro"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1016\/j.biopsych.2022.02.006","article-title":"The Amygdala Noradrenergic System Is Compromised With Alcohol Use Disorder","volume":"91","author":"Varodayan","year":"2022","journal-title":"Biol. Psychiatry"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Rodriguez, L., Kirson, D., Wolfe, S.A., Patel, R.R., Varodayan, F.P., Snyder, A.E., Gandhi, P.J., Khom, S., Vlkolinsky, R., and Bajo, M. (2022). Alcohol Dependence Induces CRF Sensitivity in Female Central Amygdala GABA Synapses. Int. J. Mol. Sci., 23.","DOI":"10.20944\/preprints202206.0234.v1"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"100547","DOI":"10.1016\/j.ynstr.2023.100547","article-title":"Glucocorticoid receptors regulate central amygdala GABAergic synapses in Marchigian-Sardinian alcohol-preferring rats","volume":"25","author":"Khom","year":"2023","journal-title":"Neurobiol. Stress"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"5170","DOI":"10.1523\/JNEUROSCI.3919-15.2016","article-title":"The Proinflammatory Cytokine Interleukin 18 Regulates Feeding by Acting on the Bed Nucleus of the Stria Terminalis","volume":"36","author":"Francesconi","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.neulet.2006.11.007","article-title":"Interleukin-18 mediated inhibition of LTP in the rat dentate gyrus is attenuated in the presence of mGluR antagonists","volume":"412","author":"Cumiskey","year":"2007","journal-title":"Neurosci. Lett."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0306-4522(01)00405-5","article-title":"The pro-inflammatory cytokine interleukin-18 impairs long-term potentiation and NMDA receptor-mediated transmission in the rat hippocampus in vitro","volume":"108","author":"Curran","year":"2001","journal-title":"Neuroscience"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.brainres.2004.03.065","article-title":"Interleukin-18 stimulates synaptically released glutamate and enhances postsynaptic AMPA receptor responses in the CA1 region of mouse hippocampal slices","volume":"1012","author":"Kanno","year":"2004","journal-title":"Brain Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1097\/00004647-200208000-00008","article-title":"Elevated intracranial IL-18 in humans and mice after traumatic brain injury and evidence of neuroprotective effects of IL-18-binding protein after experimental closed head injury","volume":"22","author":"Yatsiv","year":"2002","journal-title":"J. Cereb. Blood FlowMetab. Off. J. Int. Soc. Cereb. Blood Flow Metab."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1742-2094-1-13","article-title":"Tumor necrosis factor-mediated inhibition of interleukin-18 in the brain: A clinical and experimental study in head-injured patients and in a murine model of closed head injury","volume":"1","author":"Schmidt","year":"2004","journal-title":"J. Neuroinflammation"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.jneuroim.2003.09.005","article-title":"Identification of a truncated IL-18R beta mRNA: A putative regulator of IL-18 expressed in rat brain","volume":"145","author":"Andre","year":"2003","journal-title":"J. Neuroimmunol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1111\/adb.12256","article-title":"Chronic ethanol exposure decreases CB1 receptor function at GABAergic synapses in the rat central amygdala","volume":"21","author":"Varodayan","year":"2016","journal-title":"Addict. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1038\/npp.2011.327","article-title":"Central neuropeptide Y modulates binge-like ethanol drinking in C57BL\/6J mice via Y1 and Y2 receptors","volume":"37","author":"Sparrow","year":"2012","journal-title":"Neuropsychopharmacology"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.neuropharm.2017.01.031","article-title":"The role of neuroimmune signaling in alcoholism","volume":"122","author":"Crews","year":"2017","journal-title":"Neuropharmacology"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.biopsych.2017.01.005","article-title":"Constitutive Increases in Amygdalar Corticotropin-Releasing Factor and Fatty Acid Amide Hydrolase Drive an Anxious Phenotype","volume":"82","author":"Natividad","year":"2017","journal-title":"Biol. Psychiatry"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1126\/science.abe7199","article-title":"Sex differences in immune responses","volume":"371","author":"Takahashi","year":"2021","journal-title":"Science"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/s41586-020-2588-y","article-title":"Longitudinal analyses reveal immunological misfiring in severe COVID-19","volume":"584","author":"Lucas","year":"2020","journal-title":"Nature"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1152\/physrev.1999.79.1.1","article-title":"Regulation of the hypothalamic-pituitary-adrenal axis by cytokines: Actions and mechanisms of action","volume":"79","author":"Turnbull","year":"1999","journal-title":"Physiol. Rev."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1002\/jcp.30008","article-title":"IL-18 and infections: Is there a role for targeted therapies?","volume":"236","author":"Vecchie","year":"2021","journal-title":"J. Cell Physiol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/15\/1943\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:20:20Z","timestamp":1760127620000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/12\/15\/1943"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,27]]},"references-count":91,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["cells12151943"],"URL":"https:\/\/doi.org\/10.3390\/cells12151943","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,27]]}}}