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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.

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  • Authors+Show Affiliations

    ,

    Department of Nuclear Medicine, University Hospitals Leuven, Leuven, Belgium. koen.vanlaere@uzleuven.be

    , , , , ,

    Source

    Neurobiology of aging 33:3 2012 Mar pg 620.e1-8

    MeSH

    Aged
    Antiparkinson Agents
    Corpus Striatum
    Dopaminergic Neurons
    Female
    Humans
    Levodopa
    Limbic System
    Male
    Middle Aged
    Parkinson Disease
    Prefrontal Cortex
    Receptor, Cannabinoid, CB1
    Substantia Nigra
    Up-Regulation

    Pub Type(s)

    Comparative Study
    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    21459482

    Citation

    TY - JOUR T1 - Regional changes in type 1 cannabinoid receptor availability in Parkinson's disease in vivo. AU - Van Laere,Koen, AU - Casteels,Cindy, AU - Lunskens,Sophie, AU - Goffin,Karolien, AU - Grachev,Igor D, AU - Bormans,Guy, AU - Vandenberghe,Wim, Y1 - 2011/04/02/ PY - 2010/10/26/received PY - 2011/01/12/revised PY - 2011/02/13/accepted PY - 2011/4/5/entrez PY - 2011/4/5/pubmed PY - 2012/9/29/medline SP - 620.e1 EP - 8 JF - Neurobiology of aging JO - Neurobiol. Aging VL - 33 IS - 3 N2 - 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. SN - 1558-1497 UR - https://www.unboundmedicine.com/medline/citation/21459482/abstract/Regional_changes_in_type_1_cannabinoid_receptor_availability_in_Parkinson's_disease_in_vivo_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-4580(11)00038-8 ER -