title: Neurobehavioral abnormalities in a brain-specific NADPH-cytochrome P450 reductase knockout mouse model.
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.
authors.affiliation: Wadsworth Center, New York State Department of Health, Albany, NY 12201, United States.
authors.forename: C
authors.initials: C
authors.lastname: Fang
authors.forename: V J
authors.initials: VJ
authors.lastname: Bolivar
authors.forename: J
authors.initials: J
authors.lastname: Gu
authors.forename: W
authors.initials: W
authors.lastname: Yang
authors.forename: S O
authors.initials: SO
authors.lastname: Zeitlin
authors.forename: X
authors.initials: X
authors.lastname: Ding
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000201:enzymology*; D003214:Conditioning, Classical; D005239:Fear / Q000502:physiology*; D005260:Female; D008297:Male; D018782:Maze Learning; D008568:Memory / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009251:NADPH-Ferrihemoprotein Reductase / Q000235:genetics / Q000378:metabolism*
chemical_list: D009251:NADPH-Ferrihemoprotein Reductase