Calcium activated adenylyl cyclase AC8 but not AC1 is required for prolonged behavioral anxiety

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.