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Role of oxytocin receptors in modulation of fear by social memory

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Abstract

Rationale

Oxytocin receptors (Oxtr) are important mediators of social learning and emotion, with bidirectional effects on fear and anxiety. Contrary to the anxiolytic actions of Oxtr in the amygdala, we recently showed that Oxtr in the lateral septum mediate the enhancement of fear conditioning by social defeat in mice.

Objectives

Using positive social interactions, which impair fear conditioning, here we attempted to delineate whether the role of septal Oxtr in fear regulation depends on the valence of the social memory.

Methods

Pharmacological and genetic manipulations of lateral septal Oxtr were combined with the social buffering of fear paradigm, in which pre-exposure to nonfearful conspecifics reduces subsequent contextual fear conditioning, as revealed by decreased freezing behavior.

Results

Antagonism and down-regulation of Oxtr in the lateral septum abolished, while oxytocin (Oxt) administration before pre-exposure to nonfearful conspecifics facilitated the decrease of freezing behavior.

Conclusions

The septal oxytocin system enhances memory of social interactions regardless of their valence, reducing fear after positive and enhancing fear after negative social encounters. These findings explain, at least in part, the seemingly bidirectional role of Oxt in fear regulation.

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Acknowledgments

This research was supported by the National Institutes of Health grants R01 MH078064 (J.R.) and MH092065 (Y.F.G.). Part of this study carried out by N.K. and K.S. was the result of "Integrated research on neuropsychiatric disorder" in the Strategic Research Program for Brain Sciences by the Ministry of Education, Culture, Sports, Science, and Technology of Japan.

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Northwestern University, Chicago, IL, USA

    Yomayra F. Guzmán, Natalie C. Tronson, Ivana Mesic, Anita L. Guedea & Jelena Radulovic

  2. Department of Psychology, University of Michigan, Ann Arbor, MI, USA

    Natalie C. Tronson

  3. Department of Molecular and Cell Biology, Graduate School of Agricultural Science, Tohoku University, Tohoku, Miyagi, Japan

    Keisuke Sato & Katsuhiko Nishimori

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  1. Yomayra F. Guzmán
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  2. Natalie C. Tronson
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  3. Keisuke Sato
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  4. Ivana Mesic
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  5. Anita L. Guedea
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  6. Katsuhiko Nishimori
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  7. Jelena Radulovic
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Correspondence to Jelena Radulovic.

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Guzmán, Y.F., Tronson, N.C., Sato, K. et al. Role of oxytocin receptors in modulation of fear by social memory. Psychopharmacology 231, 2097–2105 (2014). https://doi.org/10.1007/s00213-013-3356-6

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  • DOI: https://doi.org/10.1007/s00213-013-3356-6

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