Abstract
By using a combination of positron emission tomography (PET) and postmortem tissue dissection, the effect of increased endogenous serotonin on specific binding of [11C]WAY 100635 to the 5-HT1A receptor was investigated in rat brain in vivo. The binding studies were complemented by in vivo microdialysis to monitor 5-HT levels in similarly treated isoflurane-anaesthetised rats, with the dialysis probe locations corresponding to two of the tissues sampled for specific binding of the radioligand. Fenfluramine treatment (10 mg/kg i.p.) resulted in a ∼5-fold increase in extracellular 5-HT in medial prefrontal cortex and a ∼15-fold increase in lateral hippocampus, maximal at ∼40 min after injection. PET scan duration was either 60 or 90 min, beginning 30 min after fenfluramine injection. The specific binding of [11C]WAY 100635 was reduced by 10-20% in hippocampus, which showed highest binding in control animals. Specific binding, however, was unaffected in both prefrontal cortex and midbrain raphe, each additional high binding regions. The minimal effects are consistent with a low baseline occupancy of the 5-HT1A receptor by 5-HT in vivo, so that only a large change in endogenous agonist concentration will affect radioligand binding. This implies that utilisation of [11C]WAY 100635 in human PET to quantify 5-HT1A receptor expression can be extended to pathology where synaptic 5-HT levels are altered as a consequence of the disease state.
Original language | English (US) |
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Pages (from-to) | 150-159 |
Number of pages | 10 |
Journal | Synapse |
Volume | 41 |
Issue number | 2 |
DOIs | |
State | Published - 2001 |
Externally published | Yes |
Keywords
- Endogenous serotonin
- HIDAC
- Positron emission tomography
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience