Positron emission tomography and brain monoamine neurotransmission -- entries for study of drug interactions.

Abstract

Monoamine neurotransmission is a complicated process with interactions between individual neurotransmitter pathways, multiple receptors with different responses and a variety of feedback loops regulating neurotransmitter synthesis, release, reuptake and effect on receptors. The system is further affected by a range of enzymes with co-factors controlling synthesis and degradation of monoamines. Positron emission tomography (PET) has evolved to a very versatile tool for the in vivo imaging and characterisation of physiology and biochemistry. The basis for its expansion during the last years has been a rapid development of labelling methods, allowing a range of tracer molecules to be generated and used in human and research animal studies. The most important PET radionuclide is (11)C with a short half-life of approximately 20 minutes. This radionuclide is ideal for the labelling of organic molecules and for multi-tracer applications in research and drug development studies. PET has been used for a range of explorative studies on the monoamine neurotransmission, as exemplified by studies on the expression of dopamine and serotonin receptors as well as the rate of dopamine and serotonin synthesis. The present article gives examples of studies where PET has been used for the characterization of monoamine transmitter systems in experimental animals and in humans, both in healthy individuals and in patients with diseases affecting neurotransmission.