Quantitative PET analysis of regional cerebral blood flow and glucose and oxygen metabolism in response to fenfluramine in living porcine brain.
The serotonin agonist fenfluramine has been used widely in humans for studying neuronal activation. We carried out the present study in order to determine whether anesthetized pigs could be used for studying effects of fenfluramine on cerebral functions using positron emission tomography (PET). We obtained quantitative measures of regional cerebral blood flow (rCBF) and of glucose and oxygen utilization (rCMRglc and rCMR(O2)) during intravenous administration of fenfluramine, using [15O]water, [18F]FDG and [15O]oxygen, respectively. Fenfluramine (25 mg/h i.v.) caused a significant rise in rCBF and, to a lesser extent, in rCMR2(O2), but it failed to affect rCMRglc. The findings indicate that quantitative estimation of rCBF by repeated injection of [15O]water was more sensitive than either rCMRO2 or rCMRglc for detecting effects of fenfluramine on serotonin neurotransmission in living porcine brain.
Smith
D F
DF
Institute for Basic Research in Psychiatry, Department of Biological Psychiatry, Aarhus University Psychiatric Hospital, Risskov, Denmark. dfs-mith@inet.uni2.dk
Poulsen
P H
PH
Ishizu
K
K
Sakoh
M
M
Hansen
S B
SB
Gee
A D
AD
Bender
D
D
Gjedde
A
A
D000818:Animals; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005277:Fenfluramine / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D018490:Serotonin Agents / Q000494:pharmacology*; D013552:Swine; D014055:Tomography, Emission-Computed / Q000379:methods*
D018490:Serotonin Agents; D005277:Fenfluramine; D005947:Glucose