Downregulation of Striatal Dopamine D2 Receptors in Advanced Parkinson’s Disease Contributes to the Development of Motor Fluctuation

Abstract

The purpose of this study was to evaluate the contribution of the postsynaptic mechanism to the development of motor fluctuation in advanced Parkinson’s disease (PD). We used ¹²³I-iodobenzamide single-photon emission computed tomography to measure the striatal dopamine D2 receptor densities in early levodopa-naïve PD, chronic PD with stable levodopa response, and advanced PD with fluctuating levodopa response. The basal ganglia/frontal cortex ratios at both hemispheres were calculated and averaged. PD patients with fluctuating levodopa response showed a significant decrease in striatal dopamine D2 receptor densities compared to those with early (1.57 ± 0.20 vs. 1.77 ± 0.12, p = 0.009) or chronic stable PD (1.57 ± 0.20 vs. 1.77 ± 0.10, p = 0.024). We conclude that the decreased D2 receptor densities in advanced PD reduced the ‘safety factor’ for synaptic transmission and contributed to the development of motor fluctuation.

Imaging DA release in a rat model of L-DOPA-induced dyskinesias: A longitudinal in vivo PET investigation of the antidyskinetic effect of MDMA

“…In contrast, an autoradiography study in MPTP-lesioned monkeys treated with L-DOPA for several months revealed considerably reduced striatal [ 3 H]spiperone binding compared to the levels observed in non-treated monkeys (Alexander et al, 1993). This was confirmed in a SPECT study of dyskinetic Parkinson patients, which revealed that D 2 receptor binding was reduced compared to the levels observed in patients without motor fluctuations (Hwang et al, 2002). Interestingly, a PET study with Parkinson's disease patients treated with L-DOPA over the long term found only slightly reduced [ 11 C] raclopride binding in the caudate nucleus but not in the putamen (Dentresangle et al, 1999), which is in line with our findings.…”

Clinical and [^99mTc]TRODAT-1/[¹²³I]IBZM SPECT Imaging Findings in Dopa-Responsive Dystonia

“…D2 receptor densities are normal for DRD patients. Most fluctuating idiopathic parkinsonism patients showed decreased D2 receptor densities [12, 14, 15, 16]. The finding of decreased D2 receptor densities in a patient with motor fluctuation substantiates the diagnosis of idiopathic parkinsonism.…”

“…Dopamine D2 receptor densities are reported to be normal or elevated in DRD patients [10, 11], while [ 123 I]IBZM SPECT or [ 11 C]raclopride PET have shown initial upregulation of striatal dopamine D2 receptors in the contralateral putamen of early-stage idiopathic parkinsonism [12, 13], and normal [12]or reduced [14, 15, 16]D2 receptor densities in fluctuating idiopathic parkinsonism. We report the DAT ligand [ 99m Tc]TRODAT-1 and D2 receptor ligand [ 123 I]IBZM SPECT imaging findings and the long-term treatment course in a woman with DRD for 24 years.…”

Fluctuating Cotard Syndrome in a Patient With Advanced Parkinson Disease

“…2 However, we cannot exclude that the concomitant administration of quetiapine may have further influenced the impairment of dopaminergic dysregulation, with a worsening of fluctuations, and thus might have played a supporting role in the appearance of this peculiar manifestation. 25 Finally, previous studies have been addressed to the relation between "on-off" fluctuations and neuropsychiatric disorders, [26][27][28] although the main focus of these works was the relationship between motor complications and mood disorders. 20,21 In support to this hypothesis, delusion of Cotard syndrome may respond poorly to atypical neuroleptics, commonly used in the treatment of PD psychosis, 22 while has been successfully treated enhancing dopamine activities with dopamine agonists.…”