Effect of 5-HT on binding of [11C] WAY 100635 to 5-HT1A receptors in rat brain, assessed using in vivo microdialysis and PET after fenfluramine

Erik H. Danielsen, Donald Smith, Flemming Hermansen, Albert Gjedde, Paul Cumming

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)150-159
Number of pages10
JournalSynapse
Volume41
Issue number2
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Fenfluramine
Receptor, Serotonin, 5-HT1A
Microdialysis
Positron-Emission Tomography
Serotonin
Brain
Prefrontal Cortex
Hippocampus
Injections
Isoflurane
Dissection
Dialysis
N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
Pathology

Keywords

  • Endogenous serotonin
  • HIDAC
  • Positron emission tomography

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology
  • Pharmacology

Cite this

Effect of 5-HT on binding of [11C] WAY 100635 to 5-HT1A receptors in rat brain, assessed using in vivo microdialysis and PET after fenfluramine. / Danielsen, Erik H.; Smith, Donald; Hermansen, Flemming; Gjedde, Albert; Cumming, Paul.

In: Synapse, Vol. 41, No. 2, 2001, p. 150-159.

Research output: Contribution to journalArticle

Danielsen, Erik H. ; Smith, Donald ; Hermansen, Flemming ; Gjedde, Albert ; Cumming, Paul. / Effect of 5-HT on binding of [11C] WAY 100635 to 5-HT1A receptors in rat brain, assessed using in vivo microdialysis and PET after fenfluramine. In: Synapse. 2001 ; Vol. 41, No. 2. pp. 150-159.
@article{a2aca362ce044d61851034801b21e0fe,
title = "Effect of 5-HT on binding of [11C] WAY 100635 to 5-HT1A receptors in rat brain, assessed using in vivo microdialysis and PET after fenfluramine",
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.",
keywords = "Endogenous serotonin, HIDAC, Positron emission tomography",
author = "Danielsen, {Erik H.} and Donald Smith and Flemming Hermansen and Albert Gjedde and Paul Cumming",
year = "2001",
doi = "10.1002/syn.1069",
language = "English (US)",
volume = "41",
pages = "150--159",
journal = "Synapse",
issn = "0887-4476",
publisher = "Wiley-Liss Inc.",
number = "2",

}

TY - JOUR

T1 - Effect of 5-HT on binding of [11C] WAY 100635 to 5-HT1A receptors in rat brain, assessed using in vivo microdialysis and PET after fenfluramine

AU - Danielsen, Erik H.

AU - Smith, Donald

AU - Hermansen, Flemming

AU - Gjedde, Albert

AU - Cumming, Paul

PY - 2001

Y1 - 2001

N2 - 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.

AB - 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.

KW - Endogenous serotonin

KW - HIDAC

KW - Positron emission tomography

UR - http://www.scopus.com/inward/record.url?scp=0034965148&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034965148&partnerID=8YFLogxK

U2 - 10.1002/syn.1069

DO - 10.1002/syn.1069

M3 - Article

VL - 41

SP - 150

EP - 159

JO - Synapse

JF - Synapse

SN - 0887-4476

IS - 2

ER -