An epigenetic intervention interacts with genetic strain differences to modulate the stress-induced reduction of flurazepam's antiseizure efficacy in the mouse.
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.
Deutsch
Stephen I
SI
Mental Health Service Line (116A), Department of Veterans Affairs Medical Center, 50 Irving Street, NW, Washington, DC 20422, USA. Stephen.deutsch@med.va.gov
Mastropaolo
John
J
Burket
Jessica A
JA
Rosse
Richard B
RB
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001522:Behavior, Animal; D002087:Butyrates / Q000627:therapeutic use; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004597:Electroshock / Q000009:adverse effects; D004827:Epilepsy / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D005479:Flurazepam / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D013045:Species Specificity; D013315:Stress, Psychological / Q000503:physiopathology*
D014151:Anti-Anxiety Agents; D002087:Butyrates; D018691:Excitatory Amino Acid Antagonists; D016291:Dizocilpine Maleate; D005479:Flurazepam