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Role of the IL-1 receptor antagonist in ethanol-induced regulation of GABAergic transmission in the central amygdala.
Bajo, M; Herman, M A; Varodayan, F P; Oleata, C S; Madamba, S G; Harris, R A; Blednov, Y A; Roberto, M.
Affiliation
  • Bajo M; Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: mbajo@scripps.edu.
  • Herman MA; Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA.
  • Varodayan FP; Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA.
  • Oleata CS; Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA.
  • Madamba SG; Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA.
  • Harris RA; Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, TX 78712, USA.
  • Blednov YA; Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, TX 78712, USA.
  • Roberto M; Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: mroberto@scripps.edu.
Brain Behav Immun ; 45: 189-97, 2015 Mar.
Article in En | MEDLINE | ID: mdl-25479427
The IL-1 receptor antagonist (IL-1ra), encoded by the Il1rn gene, is an endogenous antagonist of the IL-1 receptor. Studies of Il1rn knockout (KO) and wild type (WT) mice identified differences in several ethanol-related behaviors, some of which may be mediated by GABAergic transmission in the central nucleus of the amygdala (CeA). In this study we examined phasic (both evoked and spontaneous) and tonic GABAergic transmission in the CeA of Il1rn KO and WT mice and the ethanol sensitivity of these GABAergic synapses. The mean amplitude of baseline evoked GABAA-inhibitory postsynaptic potentials (IPSPs), and the baseline frequency of spontaneous GABAA-inhibitory postsynaptic currents (sIPSCs), but not the frequency of miniature GABAA-IPSCs (mIPSCs), were significantly increased in KO compared to WT mice, indicating enhanced presynaptic action potential-dependent GABA release in the CeA of KO mice. In KO mice, we also found a cell-type specific switch in the ongoing tonic GABAA receptor conductance such that the tonic conductance in low threshold bursting (LTB) neurons is lost and a tonic conductance in late spiking (LS) neurons appears. Notably, the ethanol-induced facilitation of evoked and spontaneous GABA release was lost in most of the CeA neurons from KO compared to WT mice. Ethanol superfusion increased the sIPSC rise and decay times in both KO and WT mice, suggesting ethanol-induced postsynaptic effects. The pretreatment of CeA slices with exogenous IL-1ra (Kineret; 100ng/ml) returned sIPSC frequency in KO mice to the levels found in WT. Importantly, Kineret also restored ethanol-induced potentiation of the sIPSC frequency in the KO mice. These results show that IL-1ra regulates baseline GABAergic transmission in the CeA and is critical for the ethanol effects at these synapses.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Central Nervous System Depressants / Receptors, GABA-A / Ethanol / Interleukin 1 Receptor Antagonist Protein / Inhibitory Postsynaptic Potentials / GABAergic Neurons / Gamma-Aminobutyric Acid / Amygdala Limits: Animals Language: En Journal: Brain Behav Immun Journal subject: ALERGIA E IMUNOLOGIA / CEREBRO / PSICOFISIOLOGIA Year: 2015 Document type: Article Country of publication: Netherlands

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Central Nervous System Depressants / Receptors, GABA-A / Ethanol / Interleukin 1 Receptor Antagonist Protein / Inhibitory Postsynaptic Potentials / GABAergic Neurons / Gamma-Aminobutyric Acid / Amygdala Limits: Animals Language: En Journal: Brain Behav Immun Journal subject: ALERGIA E IMUNOLOGIA / CEREBRO / PSICOFISIOLOGIA Year: 2015 Document type: Article Country of publication: Netherlands