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Effect of fenfluramine‐induced increases in serotonin release on [ 18 F]MPPF binding: A continuous infusion PET study in conscious monkeys
Author(s) -
Udo de Haes Joanna I.,
Harada Norihiro,
Elsinga Philip H.,
Maguire R. Paul,
Tsukada Hideo
Publication year - 2006
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20209
Subject(s) - fenfluramine , serotonin , pharmacology , chemistry , neuroscience , medicine , psychology , receptor , biochemistry
[ 18 F]MPPF is a selective and reversible antagonist to the serotonin‐1A (5‐HT 1A ) receptor. The aim of the present study was to investigate whether the binding of [ 18 F]MPPF is sensitive to increases in 5‐HT levels. We used the 5‐HT releasing agent and reuptake inhibitor fenfluramine (FEN) to increase the concentration of 5‐HT. [ 18 F]MPPF binding was assessed using positron emission tomography (PET) in conscious monkeys. Possible effects of blood flow on ligand binding were excluded by using a bolus‐infusion paradigm. Control scans were obtained to assess the state of ligand equilibrium. FEN (5 or 10 mg/kg, i.v.) was administered between 90 and 130 min after the start of the [ 18 F]MPPF infusion. The binding potential (BP) was calculated for an early interval (30 min preceding FEN administration) and late interval (20–50 min after administration of FEN). Microdialyses results showed a 20‐ and 35‐fold increase in extracellular 5‐HT levels in the prefrontal cortex after injection of FEN at a dose of 5 mg/kg and 10 mg/kg respectively. However, despite these large increases in 5‐HT levels, no differences in BP were found between the control and FEN scans. These results may imply that the majority of 5‐HT 1A receptors is in the low affinity state in the living brain. Synapse 59:18–26, 2006. © 2005 Wiley‐Liss, Inc.