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P5-HT1A receptors in mood and anxiety: recent insights into autoreceptor versus heteroreceptor function

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An Erratum to this article was published on 11 January 2014

Abstract

Rationale

Serotonin (5-HT) neurotransmission is intimately linked to anxiety and depression and a diverse body of evidence supports the involvement of the main inhibitory serotonergic receptor, the serotonin-1A (5-HT1A) subtype, in both disorders.

Objectives

In this review, we examine the function of 5-HT1A receptor subpopulations and re-interpret our understanding of their role in mental illness in light of new data, separating both spatial (autoreceptor versus heteroreceptor) and the temporal (developmental versus adult) roles of the endogenous 5-HT1A receptors, emphasizing their distinct actions in mediating anxiety and depression-like behaviors.

Results

It is difficult to unambiguously distinguish the effects of different populations of the 5-HT1A receptors with traditional genetic animal models and pharmacological approaches. However, with the advent of novel genetic systems and subpopulation-selective pharmacological agents, direct evidence for the distinct roles of these populations in governing emotion-related behavior is emerging.

Conclusions

There is strong and growing evidence for a functional dissociation between auto- and heteroreceptor populations in mediating anxiety and depressive-like behaviors, respectively. Furthermore, while it is well established that 5-HT1A receptors act developmentally to establish normal anxiety-like behaviors, the developmental role of 5-HT1A heteroreceptors is less clear, and the specific mechanisms underlying the developmental role of each subpopulation are likely to be key elements determining mood control in adult subjects.

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Acknowledgments

AGG is a recipient of a Spanish Ministry of Science postdoctoral fellowship. EDL is supported through NIH RO1 MH91427. We are grateful to Alex Dranovsky for helpful discussions and critical reading of the manuscript.

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  1. Department of Psychiatry, Division of Integrative Neuroscience, Columbia University and the New York State Psychiatric Institute, 1051 Riverside Dr. Box 87, New York, NY, 10032, USA

    Alvaro L. Garcia-Garcia & E. David Leonardo

  2. Neurolixis, 3210 Merryfield Ave, San Diego, CA, 92121, USA

    Adrian Newman-Tancredi

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  1. Alvaro L. Garcia-Garcia
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Correspondence to Alvaro L. Garcia-Garcia or E. David Leonardo.

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Garcia-Garcia, A.L., Newman-Tancredi, A. & Leonardo, E.D. P5-HT1A receptors in mood and anxiety: recent insights into autoreceptor versus heteroreceptor function. Psychopharmacology 231, 623–636 (2014). https://doi.org/10.1007/s00213-013-3389-x

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