title: Increased ethanol resistance and consumption in Eps8 knockout mice correlates with altered actin dynamics.
abstract: 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.
authors.affiliation: Fondazione Istituto FIRC di Oncologia Molecolare, Via Adamello 16, 20139 Milan, Italy. nina.offenhauser@ifom-ieo-campus.it
authors.forename: Nina
authors.initials: N
authors.lastname: Offenhäuser
authors.forename: Daniela
authors.initials: D
authors.lastname: Castelletti
authors.forename: Lisa
authors.initials: L
authors.lastname: Mapelli
authors.forename: Blanche Ekalle
authors.initials: BE
authors.lastname: Soppo
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Regondi
authors.forename: Paola
authors.initials: P
authors.lastname: Rossi
authors.forename: Egidio
authors.initials: E
authors.lastname: D'Angelo
authors.forename: Carolina
authors.initials: C
authors.lastname: Frassoni
authors.forename: Alida
authors.initials: A
authors.lastname: Amadeo
authors.forename: Arianna
authors.initials: A
authors.lastname: Tocchetti
authors.forename: Benedetta
authors.initials: B
authors.lastname: Pozzi
authors.forename: Andrea
authors.initials: A
authors.lastname: Disanza
authors.forename: Douglas
authors.initials: D
authors.lastname: Guarnieri
authors.forename: Christer
authors.initials: C
authors.lastname: Betsholtz
authors.forename: Giorgio
authors.initials: G
authors.lastname: Scita
authors.forename: Ulrike
authors.initials: U
authors.lastname: Heberlein
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Di Fiore
mesh_terms: D000199:Actins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000428:Alcohol Drinking; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002531:Cerebellum / Q000166:cytology; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D002492:Central Nervous System Depressants; D003598:Cytoskeletal Proteins; C083430:Eps8 protein, mouse; D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; D000431:Ethanol