Psychopharmacology

, Volume 213, Issue 2, pp 547–553

Reduced ventral striatal/ventral pallidal serotonin1B receptor binding potential in major depressive disorder

  • James W. Murrough
  • Shannan Henry
  • Jian Hu
  • Jean-Dominique Gallezot
  • Beata Planeta-Wilson
  • John F. Neumaier
  • Alexander Neumeister
Original Investigation

DOI: 10.1007/s00213-010-1881-0

Cite this article as:
Murrough, J.W., Henry, S., Hu, J. et al. Psychopharmacology (2011) 213: 547. doi:10.1007/s00213-010-1881-0

Abstract

Rationale

Although serotonin (5-HT) dysregulation is implicated in the pathophysiology of major depressive disorder (MDD), the role of specific receptor subtypes remains to be elucidated. Emerging preclinical research suggests an important role for the 5-HT1B receptor in behavioral regulation and depressive phenotypes. In particular, 5-HT1B heteroreceptors located within the striatum have been shown to play an essential role in antidepressant action.

Objectives

The objective of this study was to determine 5-HT1B receptor binding potential (BPND) in the region of the ventral striatum/ventral pallidum (VS/VP) in individuals with MDD and healthy control participants.

Methods

Ten participants with MDD (30.8 ± 9.5 years, five men/five women) in a current major depressive episode (MDE) and ten healthy control participants (30.7 ± 10.5 years, five men/five women) underwent positron emission tomography (PET) scanning with the selective 5-HT1B receptor radioligand [11C]P943.

Results

Within the VS/VP region of interest, [11C]P943 BPND was significantly reduced in the MDD group compared with the healthy control group (1.37 ± 0.13 and 1.68 ± 0.16, respectively; 18.7% between-group difference; p < 0.001).

Conclusions

Consistent with preclinical and postmortem data, our findings suggest abnormally reduced function of VS/VP 5-HT1B receptors in humans with MDD. Abnormal 5-HT1B heteroreceptor function may contribute to dysfunctional reward signaling within the striatum, including the nucleus accumbens, via interaction with dopamine, γ-amino-butyric acid, or glutamate systems. Our findings suggest reduced 5-HT1B receptor signaling in the VS/VP in MDD and contribute to the therapeutic rationale for testing 5-HT1B agonists as a novel class of antidepressants.

Keywords

Major depressive disorder Human subjects Brain imaging Serotonin Serotonin1B receptor Positron emission tomography Ventral striatum 

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • James W. Murrough
    • 1
  • Shannan Henry
    • 2
  • Jian Hu
    • 2
  • Jean-Dominique Gallezot
    • 3
  • Beata Planeta-Wilson
    • 3
  • John F. Neumaier
    • 4
  • Alexander Neumeister
    • 1
    • 2
  1. 1.Mood and Anxiety Disorders Program, Department of PsychiatryMount Sinai School of MedicineNew YorkUSA
  2. 2.Molecular Imaging Program, Clinical Neurosciences DivisionVA National Center for PTSD, VA Connecticut Healthcare SystemWest HavenUSA
  3. 3.Positron Emission Tomography Center, Department of Diagnostic RadiologyYale University School of MedicineNew HavenUSA
  4. 4.Department of PsychiatryUniversity of WashingtonSeattleUSA

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