In the ventral horn, the 5-HT axons are in close apposition to the motor neurons, especially in primates.132 In vivo imaging of the brain serotonergic systems Structural and functional tomography through the living brain is currently possible. Powerful tools, such as positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), and pharmacological MRI (phMRI),133-135 add new information on the functional anatomy of the

serotonergic systems in the human brain. PET and SPECT neuroimaging respectively use positron-emitting nuclides (18F, 11C) and gamma-emitters (123I, 125I) coupled to a small Inhibitors,research,lifescience,medical heterocyclic compound selective for one 5-HT Inhibitors,research,lifescience,medical receptor subpopulation, SERT or MAO A.87,136,137 Since the radiotracer is injected at trace level, 5-HT receptors or SERT can be localized in vivo and their relative concentration/affinity estimated from binding potential (BP). A submillimeter spatial resolution is commonly reported in PET and SPECT studies.

However, at the present time Inhibitors,research,lifescience,medical very few radiotracers selective for SERT, 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4 receptors are available.87,134,136-140 The design of new radiopharmaceuticals for in vivo imaging is constrained by several criteria including brain penetrability, target selectivity, and the absence of troublesome radiometabolites.141 Additionally, when using radiolabeled glucose Inhibitors,research,lifescience,medical analogs, PET and SPECT modalities provide information on blood flow and in some

circumstances may reflect a local activity of nervous cells following a specific pharmaceutical treatment (eg, anxiolytics, antidepressants). Offering a better spatial and temporal resolution, phMRI represents another imaging method based on the hemodynamic the response to changes in neuronal activity induced by pharmacological manipulations. This emergent imaging modality providing an indirect measure of aggregated neuronal function Inhibitors,research,lifescience,medical could have an important impact on future 5-HT research in the living human brain.133,135 Despite the limited number of available radiotracers, in vivo imaging of 5-HT function gains more and more interest in basic research as well as in clinical medicine. For example, recent publications suggest a lateralization of 5-HT1 A binding in further information language areas (auditory cortices) and sex differences in cortical and subcortical brain areas of healthy subjects.142 GSK-3 A selective interrelation between 5-HT1A distribution, sex hormones, and aggression score in humans was also demonstrated by in vivo imaging and biochemical analyses.143 More intriguingly, PET imaging studies clearly indicate that 5-HT2A receptor binding in the cortex is positively correlated to the body mass index144 and the response in painful heat stimulation.145 Furthermore, it was reported that an inverse relationship between 5-HT2A receptor and SERT BPs in the neocortex might be the result of interindividual differences in baseline 5-HT levels.