The Scripps Research Institute, USA
Michal Bajo received his PhD in 2002 from Comenius University in Bratislava, Slovakia. He undertook postdoctoral trainingin cellular physiology of addictive disorders using electrophysiological techniques at the Scripps Research Institute (TSRI) in La Jolla, California. Currently, Dr. Bajo is a staff scientist inthe Committee on the Neurobiology of Addictive Disorders at TSRI. His research includes the role of neuroimmune system in development of addiction with focus on alcohol and nicotine.
Behavioral and gene expression studies indicate that the IL-1 system is associated with alcohol drinking behavior.The GABAergic transmission in central nucleus of the amygdala (CeA) is one of the crucial mediators of alcohol addiction. Thus, wehypothesize that the IL-1 system plays an important role in alcohol effectsvia modulation of CeAGABAergicsynapses.We examined interactions betweenIL-1 systemand ethanol on GABAergic transmissionin brain slices containing CeAusing intracellular and whole-cell recordings. Superfusion of IL-1 decreased GABAergic transmission, whereas ethanolenhanced it in B6129SF2/J mice. To elucidate a role of IL-1 receptor antagonist (IL-1ra) in ethanol effects at the CeAGABAergic synapses, we usedIL-1ra knockout (KO) and wildtype (WT) mice.We found differences in baseline phasic and tonic GABA transmission between KOand WT mice.The pretreatment of CeA slices with exogenous IL-1ra (Kineret) reversed changes in the baseline phasic GABA transmission in KO mice. Superfusion of ethanol significantly enhanced GABA in majority of WT mice, whereas in KO only 50% of neurons showed an increase. The pretreatment with Kineret also restored ethanol-induced potentiation of the GABA in KO, while it had no effects in WT mice. Our results suggest that the IL-1 system is involved in a regulation of the CeAGABAergic transmissionand may modulateethanol effects at these synapses. Furthermore, IL-1 system may represent a potential therapeutic target for alcoholism.
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