Rationale: 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.
Objectives: 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.