A PET study of brain 5-HT₂ receptors and their correlation with platelet 5-HT₂ receptors in healthy humans

Abstract.

Rationale: Platelets share many properties with brain serotonergic neurons such as active 5-hydroxytryptamine (5-HT) transport, 5-HT₂ receptors, and mitochondrial monoamine oxidase. Objectives: We measured brain 5-HT₂ receptors and platelet 5-HT₂ receptors in healthy volunteers to determine if there was any correlation between the two measures. Methods: Ten healthy volunteers with no lifetime history of psychiatric illness or family history in first-degree relatives were recruited. 5-HT₂ receptor binding was determined for each subject with positron emission tomography and [¹⁸F]setoperone scan in the brain and with ³H-LSD binding in platelets. Results: We found no significant correlation between 5-HT₂ binding potential (BP) in platelets (B_max/K_d) and a semiquantitative estimate of 5-HT₂ BP in frontal, parietal, and temporal cortical regions. SPM voxel based analysis also showed no significant correlation between the 5-HT₂ BP in platelets and in the brains of the study subjects. Conclusions: Brain 5-HT₂ receptor binding was not significantly correlated to platelet ³H-LSD binding in healthy subjects. This raises questions about the validity of generalizing findings from platelet studies to 5-HT neurons in the brain.