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The Journal of Neuroscience, July 1, 2000, 20(13):4809-4820
Altered Stress-Induced Anxiety in Adenylyl Cyclase Type VIII-Deficient Mice
Michele L. Schaefer1, Scott T. Wong2, David F. Wozniak3, Lisa M. Muglia1, Jason A. Liauw4, Min Zhuo4, Anthony Nardi3, Richard E. Hartman3, Sherri K. Vogt1, Christina E. Luedke6, Daniel R. Storm2, and Louis J. Muglia1, 5 Departments of 1 Pediatrics, 3 Psychiatry, 4 Anesthesiology and Anatomy and Neurobiology, and 5 Molecular Biology and Pharmacology and Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri 63110, 2 Department of Pharmacology, University of Washington, Seattle, Washington 98195, and 6 Division of Endocrinology, Children's Hospital, Boston, Massachusetts 02115
Stress results in alterations in behavior and physiology that can be either adaptive or maladaptive. To define the molecular pathways involved in the response to stress further, we generated mice deficient (KO) in the calcium-stimulated adenylyl cyclase type VIII (AC8) by homologous recombination in embryonic stem cells. AC8 KO mice demonstrate a compromise in calcium-stimulated AC activity in the hippocampus, hypothalamus, thalamus, and brainstem. Hippocampal slices derived from AC8 KO mice fail to demonstrate CA1-region long-term depression after low-frequency stimulation, and AC8 KO mice also fail to activate CRE-binding protein in the CA1 region after restraint stress. To define the behavioral consequences of AC8 deficiency, we evaluated AC8 KO mice in the elevated plus-maze and open field. Although naïve AC8 KO mice exhibit indices of anxiety comparable with that of wild-type mice, AC8 KO mice do not show normal increases in behavioral markers of anxiety when subjected to repeated stress such as repetitive testing in the plus-maze or restraint preceding plus-maze testing. These results demonstrate a novel role for AC8 in the modulation of anxiety.
Key words: adenylyl cyclase; cAMP response element-binding protein; hippocampus; knock-out mice; long-term depression; plus-maze
Copyright © 2000 Society for Neuroscience 0270-6474/00/20134809-12$05.00/0
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