Increased ethanol resistance and consumption in Eps8 knockout mice correlates with altered actin dynamics.
Dynamic modulation of the actin cytoskeleton is critical for synaptic plasticity, abnormalities of which are thought to contribute to mental illness and addiction. Here we report that mice lacking Eps8, a regulator of actin dynamics, are resistant to some acute intoxicating effects of ethanol and show increased ethanol consumption. In ... the brain, the N-methyl-D-aspartate (NMDA) receptor is a major target of ethanol. We show that Eps8 is localized to postsynaptic structures and is part of the NMDA receptor complex. Moreover, in Eps8 null mice, NMDA receptor currents and their sensitivity to inhibition by ethanol are abnormal. In addition, Eps8 null neurons are resistant to the actin-remodeling activities of NMDA and ethanol. We propose that proper regulation of the actin cytoskeleton is a key determinant of cellular and behavioral responses to ethanol.
Mesh Terms:
Actins, Adaptor Proteins, Signal Transducing, Alcohol Drinking, Animals, Behavior, Animal, Cells, Cultured, Central Nervous System Depressants, Cerebellum, Cytoskeletal Proteins, Cytoskeleton, Ethanol, Female, Humans, Male, Mice, Mice, Knockout, Neurons, Receptors, N-Methyl-D-Aspartate, Recombinant Proteins, Signal Transduction
Actins, Adaptor Proteins, Signal Transducing, Alcohol Drinking, Animals, Behavior, Animal, Cells, Cultured, Central Nervous System Depressants, Cerebellum, Cytoskeletal Proteins, Cytoskeleton, Ethanol, Female, Humans, Male, Mice, Mice, Knockout, Neurons, Receptors, N-Methyl-D-Aspartate, Recombinant Proteins, Signal Transduction
Cell
Date: Oct. 06, 2006
PubMed ID: 17018287
View in: Pubmed Google Scholar
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