| Title | An epigenetic intervention interacts with genetic strain differences to modulate the stress-induced reduction of flurazepam's antiseizure efficacy in the mouse. | | Author(s) | Deutsch SI, Mastropaolo J, Burket JA, Rosse RB | | Institution | Mental Health Service Line (116A), Department of Veterans Affairs Medical Center, 50 Irving Street, NW, Washington, DC 20422, USA; Department of Psychiatry, Georgetown University School of Medicine, 3800 Reservoir Road, NW Washington, DC 20007, USA. | | Source | Eur Neuropsychopharmacol 2009 Feb 1. | | Abstract | Stress induces changes in the endogenous tone of both GABA and NMDA receptor-mediated neurotransmission in the intact mouse. Because changes are observed 24 h after stress, epigenetically-regulated alterations in gene expression may mediate these effects. In earlier work, sodium butyrate, a centrally-active histone deacetylase inhibitor that promotes gene expression, was shown to modulate the stress-induced reduction of the ability of MK-801 (dizocilpine), a noncompetitive NMDA receptor antagonist, to antagonize electrically-precipitated seizures. In the current study, we extended this work to look at sodium butyrate's modulatory effect on stress-induced changes in the antiseizure efficacy of flurazepam, a benzodiazepine receptor agonist, in two strains of mice. Epigenetic mechanisms, genetic strain differences and a standard stress interacted to alter flurazepam's antiseizure efficacy. These data support examination and development of epigenetic treatment strategies. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19189880 |
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