Regional changes in type 1 cannabinoid receptor availability in Parkinson's disease in vivo

Abstract

The type 1 cannabinoid receptor (CB1) is a crucial modulator of synaptic transmission in brain and has been proposed as a potential therapeutic target in Parkinson's disease (PD), especially for treatment of levodopa-induced dyskinesias (LID). Our aim was to measure CB1 levels in brains of PD patients in vivo and to investigate the relation between CB1 availability and LID. We studied 12 healthy controls and 29 PD patients (9 drug-naïve patients with early PD, 10 patients with advanced PD and LID, and 10 patients with advanced PD without LID). PD patients were examined using the Unified Parkinson's Disease Rating Scale (UPDRS) and the modified Abnormal Involuntary Movement Scale (mAIMS). All subjects underwent positron emission tomography (PET) with the CB1-selective radioligand [(18)F] MK-9470 and magnetic resonance imaging (MRI). PD patients showed an absolute decrease in CB1 availability in the substantia nigra. By contrast, CB1 availability was relatively increased in nigrostriatal, mesolimbic, and mesocortical dopaminergic projection areas. CB1 availability did not differ significantly between advanced PD patients with and without LID. Within the group of PD patients with LID, there was no significant correlation between CB1 availability and LID severity. These data demonstrate regional changes in CB1 availability in PD in vivo, but do not support a role for dysregulation of CB1 levels in the pathogenesis of LID.

Imaging in Parkinson’s Disease

“…18 F]MK-9470 has shown significant decreases in CB1R levels in the substantia nigra of early de novo and advanced PD patients with and without LIDs (van Laere et al, 2012). However, no differences were found in regional CB1R availability between advanced PD patients with and without LIDs and regional CB1R levels were not associated with LIDs severity (van Laere et al, 2012).…”

Imaging in Parkinson's Disease

“…A PET study using [ 18 F]MK-9470 has shown significant decreases in CB1R levels in the substantia nigra of early de novo and advanced PD patients with and without LIDs (van Laere et al, 2012). However, no differences were found in regional CB1R availability between advanced PD patients with and without LIDs and regional CB1R levels were not associated with LIDs severity (van Laere et al, 2012). Further studies using higher selective CB1R PET radioligands are needed in order to further elucidate the role of these receptors in the pathophysiology of PD.…”

The bright side of psychoactive substances: cannabinoid-based drugs in motor diseases

“…CB 1 receptor binding is increased in PD patients and 1-methyl-4-phenyl-1,2,3,6-tetra hydropyridine (MPTP)-treated marmosets at caudate-putamen level [17] while a decrease in CB 1 receptor availability has been observed in the SN of PD patients [18]. The eCB system undergoes a drastic remodeling during the course of PD pathogenesis.…”

“…Since there are no CB 1 receptors on DAergic neurons, the effects on DAergic transmission are indirectly mediated by CB 1 -containing GABAergic and glutamatergic neurons. This may help to understand why the eCB system results overactivated in PD as consequence of the loss of DAergic innervation and facilitation of DA-evoked motor behavior [18,23].…”