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Reduced 5-HT(2A) receptor signaling following selective bilateral amygdala damage.

Abstract
Neurobiological evidence implicates the amygdala as well as serotonergic (serotonin, 5-HT) signaling via postsynaptic 5-HT(2A) receptors as essential substrates of anxiety behaviors. Assuming a functional interdependence of these substrates, we hypothesized that a low-fear behavioral phenotype due to bilateral lesion of the amygdala would be associated with significant 5-HT(2A) receptor changes. Thus, we used [(18)F]altanserin positron emission tomography (PET) referenced to radioligand plasma levels and corrected for partial volume effects to quantify the spatial distribution of 5-HT(2A) receptor binding potential (BP(P)) in a rare patient with Urbach-Wiethe disease and selective bilateral amygdala calcification damage relative to 10 healthy control subjects. Consistent with our a priori hypothesis, we observed a 70% global decrease in 5-HT(2A) receptor BP(P) in the Urbach-Wiethe patient relative to controls. Thus, brain abnormalities in this patient are not restricted to the amygdala, but extend to overall 5-HT neurotransmission via 5-HT(2A) receptors. Our findings provide important insights into the molecular architecture of human anxiety behaviors and suggest the 5-HT(2A) receptor as a promising pharmacological target to control pathological anxiety.
AuthorsRené Hurlemann, Thomas E Schlaepfer, Andreas Matusch, Harald Reich, Nadim J Shah, Karl Zilles, Wolfgang Maier, Andreas Bauer
JournalSocial cognitive and affective neuroscience (Soc Cogn Affect Neurosci) Vol. 4 Issue 1 Pg. 79-84 (Mar 2009) ISSN: 1749-5024 [Electronic] England
PMID19015089 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Fluorine Radioisotopes
  • Radiopharmaceuticals
  • Receptor, Serotonin, 5-HT2A
  • Serotonin
  • altanserin
  • Ketanserin
Topics
  • Adult
  • Amygdala (diagnostic imaging, pathology)
  • Fluorine Radioisotopes
  • Humans
  • Image Processing, Computer-Assisted
  • Ketanserin (analogs & derivatives)
  • Lipoid Proteinosis of Urbach and Wiethe (diagnostic imaging, pathology, psychology)
  • Magnetic Resonance Imaging
  • Male
  • Neuropsychological Tests
  • Positron-Emission Tomography
  • Radiopharmaceuticals
  • Receptor, Serotonin, 5-HT2A (physiology)
  • Serotonin (physiology)
  • Synaptic Transmission

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