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Levodopa-induced dyskinesias (LIDs) are the most common and disabling adverse motor effect of therapy in Parkinson's disease (PD) patients. In this study, we investigated serotonergic mechanisms in LIDs development in PD patients using [.sup.11]C-DASB PET to evaluate serotonin terminal function and [.sup.11]C-raclopride PET to evaluate dopamine release. PD patients with LIDs showed relative preservation of serotonergic terminals throughout their disease. Identical levodopa doses induced markedly higher striatal synaptic dopamine concentrations in PD patients with LIDs compared with PD patients with stable responses to levodopa. Oral administration of the serotonin receptor type 1A agonist buspirone prior to levodopa reduced levodopaevoked striatal synaptic dopamine increases and attenuated LIDs. PD patients with LIDs that exhibited greater decreases in synaptic dopamine after buspirone pretreatment had higher levels of serotonergic terminal functional integrity. Buspirone-associated modulation of dopamine levels was greater in PD patients with mild LIDs compared with those with more severe LIDs. These findings indicate that striatal serotonergic terminals contribute to LIDs pathophysiology via aberrant processing of exogenous levodopa and release of dopamine as false neurotransmitter in the denervated striatum of PD patients with LIDs. Our results also support the development of selective serotonin receptor type 1A agonists for use as antidyskinetic agents in PD., Introduction Oral levodopa is still the most effective symptomatic treatment for Parkinson's disease (PD) patients; however, after years of daily exposure, most PD patients develop fluctuating motor responses and troublesome [...]

Abstract:: Objective: The pathogenesis of visual hallucinations (VHs) in Parkinson’s disease (PD) has been considered multifactorial. In the pathophysiology of VHs a combination of impaired visual processing and attention has been reported. Imaging studies evidenced a role of the primary visual system and visual association areas as well as a dysfunctional activation of frontal areas in the occurrence of VHs. Due to the functional connections between basal ganglia and frontal areas, a role of basal ganglia and of the fronto-striatal circuits in the pathogenesis of VHs may be postulated. Aim of this study is to unveil whether a presynaptic dopamine deficiency at baseline may predict the development of VHs. Methods: A group of 18 non demented PD patients with VHs was matched with 18 non demented PD patients without VHs as regards age of onset of disease, disease duration and severity and levodopa equivalent dose. We retrospectively analyzed the 123I-FP CIT SPECT performed on the two groups at the onset of their disease. The striatal uptake values in the two groups were examined, in order to evaluate nigrostriatal differences between the groups with different behavioral phenotype. Results: The group of patients with VHs had a significant reduction (p < 0.05) in right caudate uptake values at baseline when compared with patients without VHs. No significant differences were found between the groups regarding left caudate and putaminal uptake values. Conclusions: The frontal impairment reported in PD patients with VHs may be due to a right caudate dysfunction, as it is connected to the frontal brain areas via neuronal loops. [Copyright &y& Elsevier]

Abstract: The most challenging issue when testing putative neuroprotective agents for Parkinson''s disease (PD) in clinical trials is the assessment of the effect of the treatment on the neurodegenerative process. By measuring changes in symptoms severity, clinical rating scales represent an important tool to rate the progression of the disease. However, the rating of clinical symptoms is dependent on the examiner and the neuroprotective effect can be masked by the symptomatic effect of the therapy. 18 f-dopa PET and 123 I-β-CIT SPECT have been shown to be able to monitor the progressive loss of presynaptic nigrostriatal projections in PD and have been used as surrogate biomarkers of disease in several recent clinical trials. In this article the value of imaging as a biomarker for testing neuroprotective agents in PD is reviewed. [Copyright &y& Elsevier]

Abstract: Thirty Parkinson''s disease (PD) patients were divided into three equal groups according to their disease duration while 10 normal healthy volunteers matched for age and sex served as a control group. Striatal and extrastriatal serotonergic function was studied with 11C-DASB PET, a marker of serotonin transporter availability. 11C-DASB binding was correlated with disease disability and exposure to dopaminergic therapy. We found significant 11C-DASB binding reductions in striatal, brainstem, and cortical regions in PD but no correlations were evident between 11C-DASB binding and UPDRS scores, Hoehn &Yahr staging, disease duration and level of exposure to dopaminergic therapy. Our results suggest that progressive non-linear serotonergic dysfunction occurs in PD but it does not determine levels of disability. Additionally, chronic exposure to dopaminergic therapy does not appear to influence SERT binding. [Copyright &y& Elsevier]