ABSTRACT. There is important variation in mitochondrial function in the nucleus accumbens that explain anxiety-related differences in social competition. High anxious individuals are highly vulnerable to stress-induced depression. Importantly, high anxious rats display impaired mitochondrial function (respiration, membrane potential, ATP and ROS production) in the nucleus accumbens which is causally implicated in their disadvantage to achieve dominant status. Intra-accumbal infusion of nicotinamide, an amide form of vitamin B3 that boosts mitochondrial function, prevents the development of subordinate status in high anxious rats. Manipulations that modify anxiety levels transiently, such as acute stress or diazepam treatment, modulate social competitiveness and accumbal mitochondrial function. Notably, diazepam treatment when given either systemically or into the ventral tegmental area enhances accumbal mitochondrial respiration and ATP production along with increasing dominance behaviors. Furthermore, dominant mice show higher levels in accumbal energy-related metabolites than subordinate mice, as well as increased vulnerability to show social avoidance following social defeat. In subordinates, but not dominants, levels of these metabolites increase following chronic social defeat stress. Our findings have implications for the understanding of the mechanisms involved in individual differences in motivated behavior and vulnerability to stress.

Carmen Sandi Brain Mind Institute, Ecole Polytechnique Federal de Lausanne (EPFL), Switzerland