Abstract
Inhibitor of κB kinase (IκK) has historically been studied in the context of immune response and inflammation, but recent evidence demonstrates that IκK activity is necessary and sufficient for regulation of neuronal function. Chronic social defeat stress of mice increases IκK activity in the nucleus accumbens (NAc) and this increase is strongly correlated to depression-like behaviors. Inhibition of IκK signaling results in a reversal of chronic social defeat stress-induced social avoidance behavior. Here, we more completely define the role of IκK 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 IκK (IκKca), or a dominant negative form of IκK into the NAc. Of all three experimental groups, only mice expressing IκKca show a behavioral phenotype. Expression of IκKca 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 IκK activity alters responses to other acute stressors, we examined behavior and spine morphology in mice undergoing an acute social defeat stress. We found that IκKca enhanced social avoidance behavior and promoted thin spine formation. These data show that IκK 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.
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Acknowledgements
We thank Kevin Guise for his assistance in performing the cumulative frequency plots of average spine head volume. This work was supported by funding from the US National Institute of Mental Health (R01MH090264-01) and the National Alliance for Research on Schizophrenia and Depression (SJR).
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Christoffel, D., Golden, S., Heshmati, M. et al. Effects of Inhibitor of κB Kinase Activity in the Nucleus Accumbens on Emotional Behavior. Neuropsychopharmacol 37, 2615–2623 (2012). https://doi.org/10.1038/npp.2012.121
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DOI: https://doi.org/10.1038/npp.2012.121
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