Lack of association between the serotonin transporter and serotonin 1A receptor: an in vivo PET imaging study in healthy adults

The serotonin neurotransmitter system is modulated in part by the uptake of synaptically released serotonin (5-HT) by the serotonin transporter (5-HTT), and by specific serotonin autoreceptors such as the somatodendritic 5-HT_1A receptor, which can limit serotonin neuron depolarization. However, little is known about how 5-HTT and 5-HT_1A are related in vivo. To study this question, we reanalyzed positron emission tomography (PET) data obtained earlier in 40 healthy participants (21 females) using [¹¹C]WAY-100635 for quantification of 5-HT_1A binding and [¹¹C](+)-McN-5652 for quantification of 5-HTT binding. We hypothesized negative correlations between 5-HT_1A binding in the raphe nuclei (RN) and 5-HTT binding in RN terminal field regions. Controlling for sex, no significant correlations were found (all p>0.05). Similarly, an exploratory analysis correlating whole-brain voxel-wise 5-HTT binding with 5-HT_1A binding in RN identified no significant clusters meeting our a priori statistical threshold. The lack of correlation between 5-HT_1A and 5-HTT binding observed in the current study may be due to the different temporal responsiveness of regulatory processes controlling the somatodendritic 5-HT_1A receptor and 5-HTT in response to changing availability of intrasynaptic serotonin.