Type 1 cannabinoid receptor mapping with [18F]MK-9470 PET in the rat brain after quinolinic acid lesion: a comparison to dopamine receptors and glucose metabolism

Abstract

Purpose Several lines of evidence imply early alterations in metabolic, dopaminergic and endocannabinoid neurotransmission in Huntington's disease (HD) receptor binding were reduced in the ipsilateral caudate-putamen by 7, 35 and 77%, respectively (all p<2.10 −5 ), while an increase for these markers was observed on the contralateral side (>5%, all p<7.10 −4 ).[ 18 F]MK-9470 binding was also increased in the cerebellum (p=2.10 −5 ), where it was inversely correlated to the number of ipsiversive turnings (p=7.10 −6 ), suggesting that CB 1 receptor upregulation in the cerebellum is related to a better functional outcome. Additionally, glucose metabolism was relatively increased in the contralateral hippocampus, thalamus and sensorimotor cortex (p=1.10 −6 ). Conclusion These data point to in vivo changes in endocannabinoid transmission, specifically for CB 1 receptors in the QA model, with involvement of the caudateputamen, but also distant regions of the motor circuitry, including the cerebellum. These data also indicate the occurrence of functional plasticity on metabolism, D 2 and CB 1 neurotransmission in the contralateral hemisphere.

Comparison of Cannabinoid CB1Receptor Binding in Adolescent and Adult Rats: A Positron Emission Tomography Study Using [18F]MK-9470

“…Burns et al [34] demonstrated that the selective, high-affinity inverse agonist for the CB 1 R, named [ 18 F]MK-9470 had the potential to be a valuable tool for the in vivo study of CB 1 R biology and pharmacology. Several in vivo preclinical [35–41] and clinical studies [42–45] have used this compound successfully.…”

Excitotoxic neurodegeneration is associated with a focal decrease in metabotropic glutamate receptor type 5 availability: an in vivo PET imaging study

“…Animals had free access to pellet food and tap water, and were under a 12 h light/dark cycle. Stereotactic quinolinic acid (QA) injections into the left striatum were executed in accordance to a protocol described previously 21 . In short, animals were injected with 2 µl containing either QA (n = 10; 120 nmol dissolved in 0.9% saline solution) or saline solution (control group, n = 5), using following coordinates for the striatum: anteroposterior (AP) +0.2, lateral (LAT) +2.8, dorsoventral (DV) −4.5.…”

Methods for quantification of cerebral glycolytic metabolism using 2-deoxy-2-[18 F]fluoroglucose in small animals

“…To overcome the challenge of detecting regional changes when a global change is present, the Statistical Parametric Mapping (SPM) software was developed (Wellcome Department of Cognitive Neurology, Institute of Neurology, London, UK; Friston et al, 1994). SPM is the best-known VBA method that can be applied on a large scale in brain studies of humans and animal models of different neurological diseases or behaviours (Litaudon et al, 2017;Park et al, 2017;Cui et al, 2015;Casteels et al, 2010;Frumberg et al, 2007). SPM uses statistics to identify regions with different perfusion or metabolic rates or different volumes present in images obtained by SPECT, PET, or magnetic resonance imaging (MRI).…”