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Updated: Mar 20, 2026

Drug-induced Sensitization of Adenylyl Cyclase: Assay Streamlining and Miniaturization for Small Molecule and siRNA Screening Applications
Published on: January 27, 2014
Calcium activated adenylyl cyclase AC8 but not AC1 is required for prolonged behavioral anxiety
Matteo Bernabucci1, Min Zhuo2,3
1Department of Physiology, Faculty of Medicine, University of Toronto, University of Toronto Center for the study of pain, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada.
Background:
Anxiety disorder is a state of mental discomfort while acute anxiety induces an enhancement of vigilance/arousal or increased anxious responses. Most of the previous studies investigated basic mechanisms for acute anxiety, while less information is available for prolonged or repetitive anxiety.
Results:
In the present study, we wanted to examine possible molecular mechanisms for behavioral anxiety after repeated exposures. Performing a paradigm of five sessions of the elevated plus-maze (EPM), we show that the repeated exposure to the EPM induces a long-lasting anxiety causing a gradual increase of anxiolytic activity, which is maintained for at least 21 days. Genetic deletion of AC8 (adenylyl cyclase 8) but not AC1 abolished long-lasting anxiety.
Conclusions:
Our results suggest that calcium-stimulated AC8 is required to sustain the long-lasting anxiety caused by repeated EPM testing, and we can identify in AC8 a novel target for treating anxiety-related mood disorders.
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