title: In vivo type 1 cannabinoid receptor mapping in the 6-hydroxydopamine lesion rat model of Parkinson's disease.
abstract: Type 1 cannabinoid (CB1) receptors are expressed in high concentrations in the central nervous system, including the basal ganglia, and could have direct or indirect effects on motor behavior through modulation of dopaminergic, glutamatergic and GABA-ergic neurotransmission. Using the CB1 receptor radioligand [(18)F]MK-9470 and small-animal PET, we investigated for the first time in vivo cerebral changes in [(18)F]MK-9470 binding in the 6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease (PD), parallel to dopamine transporter (DAT) imaging, tyrosine hydroxylase (TH) staining, and behavioral measurements. In the 6-OHDA model, relative [(18)F]MK-9470 PET binding decreased in the contralateral cerebellum (-9%, p<0.0004) and caudate-putamen bilaterally (ipsilateral -8%, contralateral -7%; p=0.001 and p<0.0003, respectively). The number of TH(+) neurons in the substantia nigra was inversely correlated to CB1 receptor binding in the ipsilateral cerebellum (p=1.10(-6)). The behavioral outcome was positively related to regional CB1 receptor binding in the contralateral somatosensory cortex (p=4.10(-6)). In vivo [(18)F]MK-9470 PET imaging points to changes in endocannabinoid transmission, specifically for CB1 receptors in the 6-OHDA model of PD, with mainly involvement of the caudate-putamen, but also distant regions of the motor circuitry, including the cerebellum and somatosensory cortex.
authors.affiliation: Division of Nuclear Medicine, KU Leuven and University Hospital Leuven, Belgium. cindy.casteels@med.kuleuven.be
authors.forename: Cindy
authors.initials: C
authors.lastname: Casteels
authors.forename: Erwin
authors.initials: E
authors.lastname: Lauwers
authors.forename: Abdelbari
authors.initials: A
authors.lastname: Baitar
authors.forename: Guy
authors.initials: G
authors.lastname: Bormans
authors.forename: Veerle
authors.initials: V
authors.lastname: Baekelandt
authors.forename: Koen
authors.initials: K
authors.lastname: Van Laere
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D001931:Brain Mapping; D004195:Disease Models, Animal; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005260:Female; D009474:Neurons / Q000000981:diagnostic imaging / Q000378:metabolism; D009483:Neuropsychological Tests; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000000981:diagnostic imaging* / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011725:Pyridines; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D012720:Severity of Illness Index; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; C528731:MK-9470; D011725:Pyridines; D043884:Receptor, Cannabinoid, CB1; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase