Visualization and characterization of 5-HT receptors and transporters in vivo and in man

Ascending and descending efferent pathways from the nuclei of serotonergic neurones located in brainstem raphe nuclei project to all regions of the central nervous system. Therefore, in considering the major physiological roles played by this neurotransmitter system, it is not surprising that serotonin is implicated in the aetiologies of many CNS dysfunctions which underlie psychiatric and neurological disorders. The presynaptic serotonin uptake mechanism and the many receptor subtypes that mediate the neurotransmitter roles of serotonin have been, and continue to be, targeted by drug discovery programmes aimed at identifying improved therapies for CNS disorders. Here we review the radioligands available for the important task of visualizing and characterizing these targets in the living human brain using either positron emission tomography (PET) or single photon emission tomography (SPECT). Such studies are crucial for extending our knowledge of the involvement of serotonin neurotransmission in the aetiologies of these disorders and for the development of new and more effective therapies. Particularly important recent advances in the methodologies for imaging the 5-HT transporter, the 5-HT_2A receptor and the 5-HT_1A receptor will almost certainly lead to important clinical research into the changes occurring in serotonergic neurotransmission during the onset, progression and treatment of affective and neurodegenerative disorders.