title: Investigating the dopaminergic synapse in vivo. I. Molecular imaging studies in humans.
abstract: Dopaminergic synaptic function may be assessed either at the presynaptic terminal or at the postsynaptic binding sites using molecular in vivo imaging methods. Apart from the density of binding sites, parameters such as alterations in dopamine synthesis, dopamine storage or dopamine release can be quantified either by application of specific radiotracers or by assessing the competition between the exogenous radioligand and endogenous dopamine. Investigations of humans in both clinical and experimental settings have yielded evidence that disturbances of dopaminergic function may be associated with numerous neurological and psychiatric conditions, among which are movement disorders, schizophrenia, attention-deficit hyperactivity disorder, depression and drug abuse. This article gives an overview of those studies, which so far have been performed on dopaminergic neurotransmission in humans using in vivo imaging methods. We focus on disease-related deficiencies within the functional entity of the dopaminergic synapse. Taken together, in vivo findings yield evidence of presynaptic dysfunctions in Parkinson's disease with decreases in striatal dopamine synthesis, dopamine storage, dopamine release and dopamine transporter binding. In contrast, 'Parkinson plus' syndromes (multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration, dementia with Lewy bodies) are characterized by both pre- and postsynaptic deficiencies with reductions in striatal dopamine synthesis, dopamine storage, dopamine release, and dopamine transporter, as well as D, and D, receptor binding. In patients with Huntington's disease, postsynaptic dysfunctions with reductions of striatal D1 and D2 receptor binding have become apparent, whereas attention-deficit/ hyperactivity disorder is mainly characterized by presynaptic deficits with increases in dopamine transporter binding. Interestingly, findings are also consistent with respect to drug abuse: cocaine, amphetamine, methylphenidate, heroin, alcohol and nicotine invariably act via enhancement of dopamine release in dorsal and/ or ventral striatal regions. In vivo findings additionally suggest that not only D2 receptor binding but also the extent of dopamine release is lower in individuals with a history of drug abuse. Findings become inconsistent with increasing complexities of psychiatric conditions. As yet, there is no clear evidence as to the contributions of the individual presynaptic and postsynaptic constituents of the dopaminergic synapse to the pathophysiologies of schizophrenia and depression. As these diseases can be conceived as the result of a variety of dysfunctions and dysregulations within an intricate network of neurotransmitter systems, regional investigations of one single pre- or postsynaptic constituent may not reach far enough to disentagle the interrelationships between the constituents of one let alone a variety of neurotransmitter systems.
authors.affiliation: Clinic of Nuclear Medicine, University Hospital Düsseldorf, Germany. susanne.nikolaus@uni-duesseldorf.de
authors.forename: Susanne
authors.initials: S
authors.lastname: Nikolaus
authors.forename: Christina
authors.initials: C
authors.lastname: Antke
authors.forename: Konstantin
authors.initials: K
authors.lastname: Kley
authors.forename: Thorsten D
authors.initials: TD
authors.lastname: Poeppel
authors.forename: Hubertus
authors.initials: H
authors.lastname: Hautzel
authors.forename: Daniela
authors.initials: D
authors.lastname: Schmidt
authors.forename: Hans-Wilhelm
authors.initials: HW
authors.lastname: Müller
mesh_terms: D001921:Brain / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D001927:Brain Diseases / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D003952:Diagnostic Imaging / Q000379:methods*; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D011877:Radionuclide Imaging; D013569:Synapses / Q000378:metabolism*
chemical_list: D004298:Dopamine