title: The role of pallidal serotonergic function in Parkinson's disease dyskinesias: a positron emission tomography study.
abstract: We have investigated the role of globus pallidus (GP) serotonergic terminals in the development of levodopa-induced dyskinesias (LIDs) in Parkinson's disease (PD). We studied 12 PD patients without LIDs, 12 PD patients with LIDs, and 12 healthy control subjects. We used (11)C-DASB positron emission tomography (PET), a marker of serotonin transporter availability, and (11)C-raclopride PET to measure changes in synaptic dopamine levels following levodopa administration. PD patients without LIDs showed a significant reduction of GP serotonin transporter binding compared with healthy controls although this was within the normal range in PD patients with LIDs. Levels of GP serotonin transporter binding correlated positively with severity of dyskinesias. (11)C-raclopride PET detected a significant rise in GP synaptic dopamine levels of patients with LIDs after a levodopa challenge but not in patients with a stable response. Our findings indicate that LIDs in PD are associated with higher GP serotonergic function. This increased serotonin function may result in further dysregulation of thalamocortical signals and so promote the expression of dyskinesias.
authors: Department of Clinical Sciences, Section for Neurology, Skåne University Hospital, Lund University, Lund, Sweden; Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK.
authors: Ruben
authors: R
authors: Smith
authors: Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK.
authors: Kit
authors: K
authors: Wu
authors: Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK.
authors: Thomas
authors: T
authors: Hart
authors: Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK.
authors: Clare
authors: C
authors: Loane
authors: Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK; Positron Emission Tomography Center, Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors: David J
authors: DJ
authors: Brooks
authors: Department of Experimental Medical Sciences, Wallenberg Neuroscience Center, Lund University, Lund, Sweden.
authors: Anders
authors: A
authors: Björklund
authors: Department of Clinical Sciences, Section for Neurology, Skåne University Hospital, Lund University, Lund, Sweden; Department of Neurology, Central Hospital, Bremerhaven, Germany.
authors: Per
authors: P
authors: Odin
authors: Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK.
authors: Paola
authors: P
authors: Piccini
authors: Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK; Neurodegeneration Imaging Group, Department of Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King's College London, London, UK. Electronic address: marios.politis@kcl.ac.uk.
authors: Marios
authors: M
authors: Politis
mesh_terms: D000368:Aged; D004298:Dopamine / Q000378:metabolism; D020820:Dyskinesias / Q000209:etiology*; D005260:Female; D005917:Globus Pallidus / Q000378:metabolism*; D006801:Humans; D007980:Levodopa / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications*; D049268:Positron-Emission Tomography; D011485:Protein Binding; D059326:Serotonergic Neurons / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D012720:Severity of Illness Index; D013569:Synapses / Q000378:metabolism
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D007980:Levodopa; D004298:Dopamine
keywords: Dyskinesia; Globus pallidus; Parkinson's disease; Positron emission tomography; Serotonin