title: Mitochondrial function in the brain links anxiety with social subordination.
abstract: Dominance hierarchies are integral aspects of social groups, yet whether personality traits may predispose individuals to a particular rank remains unclear. Here we show that trait anxiety directly influences social dominance in male outbred rats and identify an important mediating role for mitochondrial function in the nucleus accumbens. High-anxious animals that are prone to become subordinate during a social encounter with a low-anxious rat exhibit reduced mitochondrial complex I and II proteins and respiratory capacity as well as decreased ATP and increased ROS production in the nucleus accumbens. A causal link for these findings is indicated by pharmacological approaches. In a dyadic contest between anxiety-matched animals, microinfusion of specific mitochondrial complex I or II inhibitors into the nucleus accumbens reduced social rank, mimicking the low probability to become dominant observed in high-anxious animals. Conversely, intraaccumbal infusion of nicotinamide, an amide form of vitamin B3 known to enhance brain energy metabolism, prevented the development of a subordinate status in high-anxious individuals. We conclude that mitochondrial function in the nucleus accumbens is crucial for social hierarchy establishment and is critically involved in the low social competitiveness associated with high anxiety. Our findings highlight a key role for brain energy metabolism in social behavior and point to mitochondrial function in the nucleus accumbens as a potential marker and avenue of treatment for anxiety-related social disorders.
authors.affiliation: Brain Mind Institute, École Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland;
authors.forename: Fiona
authors.initials: F
authors.lastname: Hollis
authors.affiliation: Brain Mind Institute, École Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland;
authors.forename: Michael A
authors.initials: MA
authors.lastname: van der Kooij
authors.affiliation: Brain Mind Institute, École Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland;
authors.forename: Olivia
authors.initials: O
authors.lastname: Zanoletti
authors.affiliation: Brain Mind Institute, École Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland;
authors.forename: Laura
authors.initials: L
authors.lastname: Lozano
authors.affiliation: Nestlé Institute of Health Sciences SA, CH-1015 Lausanne, Switzerland.
authors.forename: Carles
authors.initials: C
authors.lastname: Cantó
authors.affiliation: Brain Mind Institute, École Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland; carmen.sandi@epfl.ch.
authors.forename: Carmen
authors.initials: C
authors.lastname: Sandi
mesh_terms: D000818:Animals; D001007:Anxiety; D001921:Brain / Q000503:physiopathology*; D004291:Dominance-Subordination; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D009536:Niacinamide / Q000378:metabolism; D009714:Nucleus Accumbens / Q000503:physiopathology; D017208:Rats, Wistar; D012919:Social Behavior
chemical_list: D045222:Electron Transport Chain Complex Proteins; D009536:Niacinamide
keywords: anxiety; mitochondria; nucleus accumbens; social competition; social dominance