Electrophysiological and Behavioral Responses to Ketamine in Mice with Reduced Akt1 Expression

Overview

Journal Psychopharmacology (Berl)

Specialty Pharmacology

Date 2013 Feb 9

PMID 23392353

Citations 9

Authors

Robert E Featherstone

Valerie M Tatard-Leitman

Jimmy D Suh

Robert Lin

Irwin Lucki

Steven J Siegel

Affiliations

Soon will be listed here.

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.

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