Serotonin receptors and neurodegenerative processes. A Focus on 5-HT1A receptor PET imaging
Serotonin (5-hydroxytryptamine, 5 HT) and its various receptors are involved in numerous central nervous system functions.
Among the currently known 5-HT receptors, the 5-HT1A receptor is the best characterized subtype, tightly implicated in the pathogenesis of mood disorders.
Recent preclinical and clinical studies suggest that 5-HT1A receptors are involved in cognitive impairments during Alzheimer’s disease or Parkinson’s disease and may constitute a possible therapeutic target. Receptors can be visualized and quantified postmortem by autoradiography and in vivo by positron emission tomography (PET), facilitating the translation from animal research to man. However, these imaging studies of 5-HT1A receptors have produced conflicting results. One explanation of these discrepant findings could be that all PET studies used radiolabelled antagonists which bind unspecifically to functional 5-HT1A receptors, pharmacologically mobilizable, and to non-functional receptors. The use of PET 5-HT1A agonists could therefore provide a measure of the remaining functional receptors during the neurodegenerative processes.
Although questions are still pending regarding the correlation between 5-HT1A functional state at a pathophysiological process and the following therapeutic efficacy, this approach illustrates the potential value of PET pharmaco-imaging.

Luc ZIMMER, CRNL/Bioran