Mitochondria as pharmacological targets for anxiolytic treatment

Current treatment strategies for anxiety disorders are predominantly symptom-based. A third of anxiety patients remain unresponsive to anxiolytics highlighting the need for more effective, mechanism-based therapeutic approaches. We have previously compared high vs. low anxiety mice and identified changes in mitochondrial pathways, including oxidative phosphorylation and oxidative stress [1,2]. Here, we show that selective pharmacological targeting of these mitochondrial pathways exerts anxiolytic effects in vivo. High anxiety mice were treated with MitoQ, an antioxidant that selectively targets mitochondria [3]. MitoQ administration resulted in decreased anxiety-related behavior. We then investigated the molecular underpinnings of the MitoQ-driven anxiolytic effect and found alterations in brain and plasma of MitoQ-treated vs. untreated mice and of MitoQ responders vs. non-responders. Our findings indicate that a mechanism-driven approach based on selective mitochondrial targeting attenuates the high anxiety phenotype in vivo and pave the way for future translational implementation as long-term MitoQ administration is well-tolerated with no side-effects in mice and humans. This study was supported by DFG