Correlation between serotonin synthesis and 5-HT1A receptor binding in the living human brain: a combined alpha-[11C]MT and [18F]MPPF positron emission tomography study.
Serotonin (5-HT) is one of the major neurotransmitters and has been implicated in a wide variety of cerebral functions. Several lines of evidence indicate that 5HT(1A) receptors exert a negative feedback in the synthesis and release of serotonin. While most of what is known about serotonin comes from studies in animals, much less empirical evidence exists about the serotonergic system in the living human brain. This study aims to assess the correlation between serotonin synthesis and 5-HT(1A) receptor binding using positron emission tomography (PET) in humans. Six healthy male volunteers underwent 2 PET scans in the same day: one measuring alpha-[(11)C]MT K [ml/g/min] trapping constant (a measure of serotonin synthesis) and one measuring 5-HT(1A) receptor binding potential BP(ND) with [(18)F]MPPF. Volumes of interest (VOIs) selected a priori included: anterior cingulate cortex (ACC), anterior insula, hippocampus, amygdala, thalamus, hypothalamus and midbrain raphe nuclei. Correlation analyses were conducted voxel-by-voxel and with manually traced VOIs. A significant negative correlation between serotonin synthesis and 5-HT(1A) binding potential was found bilaterally in hippocampus and anterior insula and in the left ACC. The combination of [(18)F]MPPF and alpha-[(11)C]MT PET offers a means to investigate key determinants of 5-HT neurotransmission under physiological and psychopathological conditions in the human brain in vivo.
Frey
Benicio N
BN
McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada H3A 2B4.
Rosa-Neto
Pedro
P
Lubarsky
Stuart
S
Diksic
Mirko
M
D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D010879:Piperazines / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding; D011725:Pyridines / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D013223:Statistics as Topic; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
C114151:4-fluoro-N-(2-(1-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-2-pyridinylbenzamide; D010879:Piperazines; D011725:Pyridines; D019275:Radiopharmaceuticals; D044282:Receptor, Serotonin, 5-HT1A; C020774:alpha-methyltryptophan; D012701:Serotonin; D014364:Tryptophan