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

Research output: Contribution to journalArticlepeer-review

98 Scopus citations


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 (BP ND) 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 BP ND 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.

Original languageEnglish
Pages (from-to)547-553
Number of pages7
Issue number2-3
StatePublished - Feb 2011


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


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