Effects of Inhibitor of κB Kinase Activity in the Nucleus Accumbens on Emotional Behavior

Inhibitor of kappa B kinase (vertical bar kappa K) has historically been studied in the context of immune response and inflammation, but recent evidence demonstrates that vertical bar kappa K activity is necessary and sufficient for regulation of neuronal function. Chronic social defeat stress of mice increases vertical bar kappa K activity in the nucleus accumbens (NAc) and this increase is strongly correlated to depression-like behaviors. Inhibition of vertical bar kappa K signaling results in a reversal of chronic social defeat stress-induced social avoidance behavior. Here, we more completely define the role of vertical bar kappa K in anxiety and depressive-like behaviors. Mice underwent stereotaxic microinjection of a herpes simplex virus expressing either green fluorescent protein, a constitutively active form of vertical bar kappa K (vertical bar kappa Kca), or a dominant negative form of vertical bar kappa K into the NAc. Of all three experimental groups, only mice expressing vertical bar kappa Kca show a behavioral phenotype. Expression of vertical bar kappa Kca results in a decrease in the time spent in the non-periphery zones of an open field arena and increased time spent immobile during a forced swim test. No baseline differences in sucrose preference were observed, but following the acute swim stress we noted a marked reduction in sucrose preference. To determine whether vertical bar kappa K activity alters responses to other acute stressors, we examined behavior and spine morphology in mice undergoing an acute social defeat stress. We found that vertical bar kappa Kca enhanced social avoidance behavior and promoted thin spine formation. These data show that vertical bar kappa Kca in NAc is a critical regulator of both depressive- and anxiety-like states and may do so by promoting the formation of immature excitatory synapses. Neuropsychopharmacology (2012) 37, 2615-2623; doi:10.1038/npp.2012.121; published online 11 July 2012