A PET study on regional coexpression of 5-HT1A receptors and 5-HTT in the human brain.
BACKGROUND
Several lines of evidence suggest inter-dependency between the serotonin transporter (5-HTT) and the 5HT1A receptor, two recognised targets for the treatment of anxiety and depression.


OBJECTIVE
to examine the correlation of regional expression levels for these two serotonergic markers in the human brain in vivo.


METHODS
Twelve male control subjects were examined with PET twice on the same day, using the radioligands [11C]WAY 100635 and [11C]MADAM for quantification of the 5-HT1A receptor and the 5-HTT, respectively. The binding potential (BP) was calculated for raphe nuclei, hippocampus and frontal cortex.


RESULTS
In all regions, the BP for both [11C]WAY 100635 (raphe nuclei 1.85-4.71, hippocampus 2.52-6.17, frontal cortex 2.03-3.79) and [11C]MADAM (2.70-7.65, 0.47-1.76, 0.18-0.51) varied several fold between subjects. In the raphe nuclei, where the two markers are situated on the same neurons, the ratio of [11C]WAY 100635 binding to [11C]MADAM BP binding varied considerably (0.43-1.05). There was a positive correlation between the two markers in the raphe nuclei (rxy=0.68, p<0.05) and in the hippocampus (rxy=0.97, p<0.001) but not in the frontal cortex (rxy=-0.25, p=0.44).


CONCLUSIONS
The results support a correlation between density levels of the 5-HT1A-receptor and the 5-HTT in the raphe nuclei and hippocampus but not in the frontal cortex. A suggested clinical implication is that the inter-individual variability in 5-HT1A-receptor and 5-HTT densities, as well as the ratio of these, is of particular interest in relation to individual responses to selective serotonin reuptake inhibitor treatment.
Lundberg
Johan
J
Department of Clinical Neuroscience, Section of Psychiatry, Karolinska Institutet, Stockholm, Sweden. johan.lundberg@ki.se
Borg
Jacqueline
J
Halldin
Christer
C
Farde
Lars
L
D000328:Adult; D001596:Benzylamines; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes; D005625:Frontal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines; D049268:Positron-Emission Tomography; D011725:Pyridines; D019275:Radiopharmaceuticals; D011903:Raphe Nuclei / Q000000981:diagnostic imaging / Q000378:metabolism; D044282:Receptor, Serotonin, 5-HT1A / Q000096:biosynthesis*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000096:biosynthesis*
D001596:Benzylamines; D002250:Carbon Radioisotopes; C470437:N,N-dimethyl-2-(2-amino-4-methylphenylthio)benzylamine; D010879:Piperazines; D011725:Pyridines; D019275:Radiopharmaceuticals; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide