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Fear-enhancing effects of septal oxytocin receptors


The nonapeptide oxytocin is considered beneficial to mental health due to its anxiolytic, prosocial and antistress effects, but evidence for anxiogenic actions of oxytocin in humans has recently emerged. Using region-specific manipulations of the mouse oxytocin receptor (Oxtr) gene (Oxtr), we identified the lateral septum as the brain region mediating fear-enhancing effects of Oxtr. These effects emerge after social defeat and require Oxtr specifically coupled to the extracellular signal–regulated protein kinase pathway.

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Figure 1: Oxtr mediates the enhancement of fear by social-defeat stress.
Figure 2: Coupling of lateral septal Oxtr to Erk-1/2 signaling.

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This research was supported by US National Institutes of Health grants R01 MH078064 (J.R.) and MH092065 (Y.F.G.). Part of this study carried out by K.N. and K.S. was the result of “Molecular study of the functional mechanism of oxytocin in brain” carried out under the Strategic Research Program for Brain Sciences by the Ministry of Education, Culture, Sports, Science and Technology of Japan. We thank P. Osten (Cold Spring Harbor) for providing the rAAV-Cre vector, and L. Li and W.G. Tourtellotte (Department of Pathology, Northwestern University) for providing B6.129S4-Gt(ROSA) mice and their help with the β-galactosidase staining.

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Y.F.G. performed all of the experiments and data analyses, Y.F.G. and J.R. designed the studies and wrote the paper, K.S., H.M. and K.N. developed the rAAV-Oxtr and rAAV-GFP viral vectors, K.N. provided the OxtrloxP/loxP and Venus reporter mice, N.C.T. developed the model of social defeat, V.J. helped with the quantitative PCR analyses, and A.L.G. bred and genotyped the mice.

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Correspondence to Jelena Radulovic.

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The authors declare no competing financial interests.

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Guzmán, Y., Tronson, N., Jovasevic, V. et al. Fear-enhancing effects of septal oxytocin receptors. Nat Neurosci 16, 1185–1187 (2013).

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