Pharmacopsychiatry 2015; 25 - A43
DOI: 10.1055/s-0035-1557981

Mitochondria as pharmacological targets for anxiolytic treatment

M Nussbaumer 1, J M Asara 2, L Teplytska 1, M P Murphy 3, R Landgraf 1, C W Turck 1, M D Filiou 1
  • 1Max Planck Institute of Psychiatry, Munich, Germany
  • 2Harvard Medical School, Boston, MA
  • 3MRC, Mitochondrial Biology Unit, Cambridge, United Kingdom

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

References

[1] Filiou et al, Biol Psychiatry 2011; 70:1074–82 [2] Filiou et al, J Psychiatr Res 2014; 58:115–22 [3] Smith and Murphy Ann N Y Acad Sci 2010; 1201:96–103