Molecular Neurobiology

, Volume 43, Issue 3, pp 228–253 | Cite as

Role of the 5-HT7 Receptor in the Central Nervous System: from Current Status to Future Perspectives

  • Anne Matthys
  • Guy Haegeman
  • Kathleen Van CraenenbroeckEmail author
  • Peter Vanhoenacker


Pharmacological and genetic tools targeting the 5-hydroxytryptamine (5-HT)7 receptor in preclinical animal models have implicated this receptor in diverse (patho)physiological processes of the central nervous system (CNS). Some data obtained with 5-HT7 receptor knockout mice, selective antagonists, and, to a lesser extent, agonists, however, are quite contradictory. In this review, we not only discuss in detail the role of the 5-HT7 receptor in the CNS but also propose some hypothetical models, which could explain the observed inconsistencies. These models are based on two novel concepts within the field of G protein-coupled receptors (GPCR), namely biphasic signaling and G protein-independent signaling, which both have been shown to be mediated by GPCR dimerization. This led us to suggest that the 5-HT7 receptor could reside in different dimeric contexts and initiate different signaling pathways, depending on the neuronal circuitry and/or brain region. In conclusion, we highlight GPCR dimerization and G protein-independent signaling as two promising future directions in 5-HT7 receptor research, which ultimately might lead to the development of more efficient dimer- and/or pathway-specific therapeutics.


5-HT7 receptor Circadian rhythm REM sleep Depression Thermoregulation Anxiety Schizophrenia Pain Substance abuse Memory 



K. Van Craenenbroeck has a postdoctoral fellowship from Fonds voor Wetenschappelijk Onderzoek (FWO).


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Anne Matthys
    • 1
  • Guy Haegeman
    • 1
  • Kathleen Van Craenenbroeck
    • 1
    Email author
  • Peter Vanhoenacker
    • 2
  1. 1.Laboratory of Eukaryotic Gene Expression and Signal Transduction (LEGEST), Department of PhysiologyGhent University (UGent)GhentBelgium
  2. 2.ActoGeniX NVZwijnaardeBelgium

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