1. Increased Ethanol Resistance and Consumption in Eps8 Knockout Mice Correlates with Altered Actin Dynamics
- Author
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Arianna Tocchetti, Ulrike Heberlein, Blanche Ekalle Soppo, Andrea Disanza, Christer Betsholtz, Daniela Castelletti, Paola Rossi, Douglas J. Guarnieri, Giorgio Scita, Benedetta Pozzi, Carolina Frassoni, Egidio D'Angelo, Nina Offenhäuser, Pier Paolo Di Fiore, Lisa Mapelli, Maria Cristina Regondi, and Alida Amadeo
- Subjects
Biochemistry, Genetics and Molecular Biology(all) ,Regulator ,macromolecular substances ,Biology ,Actin cytoskeleton ,General Biochemistry, Genetics and Molecular Biology ,Cell biology ,EPS8 ,Biochemistry ,Postsynaptic potential ,Synaptic plasticity ,Knockout mouse ,NMDA receptor ,Receptor - Abstract
SUMMARY 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-Daspartate (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.
- Published
- 2006
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