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Social deficits in the AY-9944 mouse model of atypical absence epilepsy.

Abstract
Atypical absence epilepsy (AAE) showing slow spike-and-wave discharges (SWD) is characterized by severely abnormal cognition and neurodevelopmental or neurological outcomes in humans. However, despite the severe behavioral outcomes in AAE, the relationship between AAE and social-behavioral dysfunctions has not defined well, either experimentally or in patients with AAE. Experimentally, AAE can be produced by administering AY-9944 (AY), a cholesterol biosynthesis inhibitor. In this study, we characterized social behavior in the AY mouse model of AAE. AAE in the mouse was induced by repeated postnatal administration of AY every 6 days from postnatal day (P) 2 to P20. AY-treated mice exhibited spontaneous, recurrent, and synchronous SWD (4-5 Hz) in electroencephalographic recordings. AY-treated mice performed tasks involving sociability/social novelty preference, social interaction with a juvenile conspecific, observational fear, and resident-intruder aggression. They showed behavioral dysfunction in social interactions with a juvenile conspecific and sociability/social novelty preference tasks. They also exhibited reduced social fear learning in observational fear conditioning. Interestingly, they showed increased levels of offensive behaviors in a resident-intruder task. However, AY-treated mice displayed normal levels of anxiety in light/dark transition and the elevated plus maze tasks, and showed slightly increased locomotor activity in an open-field task. These results demonstrate social dysfunction in the AY-induced AAE model. Our study of social behavior can also provide valuable information about Lennox-Gastaut syndrome, in which AAE is a component. Thus, our findings may help to understand behavioral pathogenesis or characteristics of patients with AAE.
AuthorsSeungmoon Jung, Jin Soo Seo, Byung Sun Kim, Doheon Lee, Keun-Hwa Jung, Kon Chu, Sang Kun Lee, Daejong Jeon
JournalBehavioural brain research (Behav Brain Res) Vol. 236 Issue 1 Pg. 23-29 (Jan 01 2013) ISSN: 1872-7549 [Electronic] Netherlands
PMID22944514 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 Elsevier B.V. All rights reserved.
Chemical References
  • trans-1,4-Bis(2-chlorobenzaminomethyl)cyclohexane Dihydrochloride
Topics
  • Aggression (drug effects, psychology)
  • Animals
  • Anxiety (psychology)
  • Conditioning, Operant (drug effects)
  • Electrodes, Implanted
  • Electroencephalography (drug effects)
  • Electrophysiology
  • Epilepsy, Absence (chemically induced, psychology)
  • Exploratory Behavior (drug effects)
  • Fear (psychology)
  • Interpersonal Relations
  • Learning (drug effects)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Smell (drug effects)
  • Social Behavior
  • trans-1,4-Bis(2-chlorobenzaminomethyl)cyclohexane Dihydrochloride

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