Psychopharmacology

, Volume 227, Issue 4, pp 639–649 | Cite as

Electrophysiological and behavioral responses to ketamine in mice with reduced Akt1 expression

  • Robert E. Featherstone
  • Valerie M.Tatard-Leitman
  • Jimmy D. Suh
  • Robert Lin
  • Irwin Lucki
  • Steven J. Siegel
Original Investigation

Abstract

Rationale

A number of studies have associated reduced Akt1 expression with vulnerability for schizophrenia. Although mice with deletion of a single copy of the Akt1 gene (Akt1+/−) show reduced Akt1 expression relative to wild-type (WT) animals, the extent to which these mice show schizophrenia-like phenotypic changes and/or increased susceptibility to epigenetic or non-genetic factors related to schizophrenia is unknown.

Objectives

Mutant mice were assessed on electroencephalographic/event-related potential (EEG/ERP) and behavioral (acoustic startle and pre-pulse inhibition) measures relevant to schizophrenia. Mice were also assessed following exposure to the NMDA receptor antagonist ketamine, a potent psychotomimetic drug, in order to assess the role of reduced Akt1 expression as a vulnerability factor for schizophrenia. Methods Akt1+/−, Akt1−/−, and WT mice received a series of paired-click, white noise stimuli, following ketamine (50 mg/kg) and saline injections. EEG was analyzed for ERPs and event-related power. Akt1+/− and WT mice were also assessed on PPI following ketamine (50 mg/kg) or saline injection.

Results

Akt1+/− and Akt1−/− mice displayed reduced amplitude of the P20 component of the ERP to the first click of a paired-click stimulus, as well as reduced S1–S2 difference for P20 and N40 components, following ketamine. Mutant mice also showed increased reduction in gamma synchrony and theta suppression following ketamine. Akt1+/− mice displayed reduced pre-pulse inhibition.

Conclusions

Reduced genetic expression of Akt1 facilitated ketamine-induced changes of EEG and behavior in mice, suggesting that reduced Akt1 expression can serve as a vulnerability factor for schizophrenia.

Keywords

Schizophrenia ERSP ITC P50 N100 Evoked-potential Gamma Theta Ketamine Drug abuse 

Supplementary material

213_2013_2997_MOESM1_ESM.docx (97 kb)
ESM 1(DOCX 97 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Robert E. Featherstone
    • 1
  • Valerie M.Tatard-Leitman
    • 1
  • Jimmy D. Suh
    • 1
  • Robert Lin
    • 1
  • Irwin Lucki
    • 2
    • 3
  • Steven J. Siegel
    • 1
  1. 1.Department of Psychiatry, Translational Neuroscience Program, School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  2. 2.Department of Psychiatry, School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  3. 3.Department of Pharmacology, School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA

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