Quantification of the Cannabinoid Type 1 Receptor Availability in the Mouse Brain

Abstract

Introduction: The endocannabinoid system is involved in several diseases such as addictive disorders, schizophrenia, post-traumatic stress disorder, and eating disorders. As often mice are used as the preferred animal model in translational research, in particular when using genetically modified mice, this study aimed to provide a systematic analysis of in vivo cannabinoid type 1 (CB1) receptor ligand-binding capacity using positron emission tomography (PET) using the ligand [18F]MK-9470. We then compared the PET results with literature data from immunohistochemistry (IHC) to review the consistency between ex vivo protein expression and in vivo ligand binding.Methods: Six male C57BL/6J (6–9 weeks) mice were examined with the CB1 receptor ligand [18F]MK-9470 and small animal PET. Different brain regions were evaluated using the parameter %ID/ml. The PET results of the [18F]MK-9470 accumulation in the mouse brain were compared with immunohistochemical literature data.Results: The ligand [18F]MK-9470 was taken up into the mouse brain within 5 min after injection and exhibited slow kinetics. It accumulated highly in most parts of the brain. PET and IHC classifications were consistent for most parts of the telencephalon, while brain regions of the diencephalon, mesencephalon, and rhombencephalon were rated higher with PET than IHC.Conclusions: This preclinical [18F]MK-9470 study demonstrated the radioligand’s applicability for imaging the region-specific CB1 receptor availability in the healthy adult mouse brain and thus offers the potential to study CB1 receptor availability in pathological conditions.

Endocannabinoid system and eating behavior / Sistema endocannabinoide y conducta alimentaria

“…It is worth mentioning that Miederer et al determined the distribution of CB1R in the brain of young adult mice, using the agonist [ 18 F] MK-9470 and monitoring by PET. It was confirmed that the CB1R is distributed in the brain, and that there is a higher expression in regions such as the telencephalon, diencephalon, midbrain, and hindbrain in healthy adult mice (Miederer et al, 2020). Casteels et al corroborated the involvement of the CB1R in mood disorders in a rat model of anorexia nervosa and performed in vivo brain mapping using the CB1R ligand [ 18 F]MK-9470 and following the signal by PET; it was found that female rats have affected the CB1R mainly in the hippocampus, which was reversible after disappearance of the anorexia nervosa (Casteels et al, 2014).…”

Chronic exposure to inhaled vaporized cannabis high in Δ9-THC alters brain structure in adult female mice

“…In contrast, Battistella et al (2014) reported long-term cannabis use in healthy men 18–30 years of age was also associated with a reduction in gray matter volume in many areas of the cerebral cortex as shown here with adult female mice. These authors suggested the change in volume was mediated by the high density of CB1 receptors in the human cortex ( Herkenham et al, 1990 ) which is also true in mice ( Miederer et al, 2020 ).…”

Hippocampal expression of the cannabinoid receptor type 1 in canine epilepsy

“…It would be also advantageous to validate those results using another methodology-although studies in animal preclinical models indicate that CB1R availability measured by means of positron emission tomography (PET) and IHC were consistent in telencephalon, in other brain parts PET indicated higher activation than IHC data 53 .…”