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Serotonin1A receptor acts during development to establish normal anxiety-like behaviour in the adult

Nature volume 416, pages 396–400 (2002)Cite this article

Abstract

Serotonin is implicated in mood regulation, and drugs acting via the serotonergic system are effective in treating anxiety and depression. Specifically, agonists of the serotonin1A receptor have anxiolytic properties, and knockout mice lacking this receptor show increased anxiety-like behaviour. Here we use a tissue-specific, conditional rescue strategy to show that expression of the serotonin1A receptor primarily in the hippocampus and cortex, but not in the raphe nuclei, is sufficient to rescue the behavioural phenotype of the knockout mice. Furthermore, using the conditional nature of these transgenic mice, we suggest that receptor expression during the early postnatal period, but not in the adult, is necessary for this behavioural rescue. These findings show that postnatal developmental processes help to establish adult anxiety-like behaviour. In addition, the normal role of the serotonin1A receptor during development may be different from its function when this receptor is activated by therapeutic intervention in adulthood.

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Figure 1: Genetic rescue strategy and 5-HT1AR expression.
Figure 2: Functional 5-HT1AR in the hippocampus, but not in raphe nuclei of rescue mice.
Figure 3: Anxiety-like behaviour in the rescue mice is normal.
Figure 4: Turning off 5-HT1AR in the adult does not alter anxiety-like behaviour.
Figure 5: Turning off 5-HT1AR during development is sufficient to reverse the rescue phenotype.
Figure 6: Expression of the 5-HT1AR during development by 125I-MPPI receptor autoradiography24.

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Acknowledgements

We thank I. Mendez for her help with mouse husbandry and behavioural analysis. This research was supported by grants from NIMH (C.G., S.B., R.H.), NINDS (S.B.), NIDA (R.H.), and NARSAD (X.Z., L.S., R.H.).

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Author notes

  1. Xiaoxi Zhuang

    Present address: Department of Neurobiology, Pharmacology, and Physiology, University of Chicago, Illinois, 60637, USA

  2. Cornelius Gross and Xiaoxi Zhuang: These authors contributed equally to the work

Authors and Affiliations

  1. Center for Neurobiology and Behavior, Columbia University, New York, 10032, USA

    Cornelius Gross, Xiaoxi Zhuang, Kimberly Stark, Sylvie Ramboz, Ronald Oosting, Luca Santarelli & René Hen

  2. Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, 19104, USA

    Lynn Kirby & Sheryl Beck

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  1. Cornelius Gross
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Correspondence to René Hen.

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Gross, C., Zhuang, X., Stark, K. et al. Serotonin1A receptor acts during development to establish normal anxiety-like behaviour in the adult. Nature 416, 396–400 (2002). https://doi.org/10.1038/416396a

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