Neurobehavioral abnormalities in a brain-specific NADPH-cytochrome P450 reductase knockout mouse model

C. Fang, V. J. Bolivar, J. Gu, W. Yang, S. O. Zeitlin, X. Ding

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

The aim of the present study was to test a new hypothesis that brain cytochrome P450 reductase (CPR) and CPR-dependent enzymes play important roles in behavioral performance. A mouse model with brain neuron-specific deletion of the Cpr gene (brain-Cpr-null) was recently generated. Brain-Cpr-null mice and wild-type (WT) littermates were compared in a variety of behavioral assays. Notable differences were found in the exploratory behavior assay: for both males and females, activity in the center of the chamber was significantly higher for brain-Cpr-null than for WT mice on days 2 and 3 of the assay, although no significant difference was found between the two groups in anxiety-like behavior in the elevated zero maze. Furthermore, in the fear-conditioning assay, brain-Cpr-null mice exhibited significantly less activity suppression than did WT controls. This deficit in activity suppression was not accompanied by any difference between WT and brain-Cpr-null mice in nociceptive responses to foot shocks. Abnormal activity suppression was also observed in both male and female brain-Cpr-null mice during the contextual memory test. However, in the Morris water maze assay, the brain-Cpr-null and WT mice were indistinguishable, indicating normal spatial memory in the mutant mice. These data collectively indicate a novel role of the Cpr gene in fear conditioning and memory.

Original languageEnglish (US)
Pages (from-to)170-180
Number of pages11
JournalNeuroscience
Volume218
DOIs
StatePublished - Aug 30 2012
Externally publishedYes

Keywords

  • Brain
  • Cytochrome P450
  • Fear conditioning
  • Memory
  • Mice
  • NADPH-cytochrome P450 reductase

ASJC Scopus subject areas

  • Neuroscience(all)

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