title: Circadian variation of metabotropic glutamate receptor 5 availability in the rat brain.
abstract: The metabotrophic subtype 5 glutamate receptor (mGluR5) plays a critical role in synaptic plasticity besides its involvement in numerous neurological disorders, such as depression. As mGluR5 availability in humans is altered in sleep deprivation, we hypothesized that mGluR5 availability underlies a circadian variation. To investigate whether mGluR5 underlies potential circadian changes we measured its density in a randomized fashion at six different daytimes in 11 adult Sprague-Dawley rats. mGluR5 density was quantified by positron emission tomography (PET) using the radioactive ligand [11C]ABP688. [11C]ABP688 uptake was quantified in nine regions of interest with a reference tissue model. Significant differences in the binding potential (BPND) and therefore mGluR5 availability between the different circadian times were found in cortex, cingulate cortex, amygdala, caudate putamen and nucleus accumbens. Further post-hoc statistical analysis (Tukey-Kramer test) of the different time-points revealed significant changes in BPNDbetween 07:00 hours (start of light-on phase) and 15:00 hours (last time-point of the light-on phase) in the caudate putamen. This study shows that mGluR5 availability is increased during the light-on, or sleep phase, of rodents by approximately 10%. Given that altered mGluR5 densities play a role in psychiatric disorders, further investigation is warranted to evaluate their circadian involvement in mood changes in humans.
authors.affiliation: Institute of Neuroscience and Medicine, INM-2, Forschungszentrum Jülich, Jülich, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Elmenhorst
authors.affiliation: Institute of Neuroscience and Medicine, INM-2, Forschungszentrum Jülich, Jülich, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Mertens
authors.affiliation: Institute of Neuroscience and Medicine, INM-2, Forschungszentrum Jülich, Jülich, Germany.
authors.forename: Tina
authors.initials: T
authors.lastname: Kroll
authors.affiliation: Institute of Neuroscience and Medicine, INM-2, Forschungszentrum Jülich, Jülich, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Oskamp
authors.affiliation: Institute of Neuroscience and Medicine, INM-5, Forschungszentrum Jülich, Jülich, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Ermert
authors.affiliation: Institute of Aerospace Medicine, German Aerospace Center, Cologne, Germany.
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Elmenhorst
authors.affiliation: Institute of Neuroscience and Medicine, INM-2, Forschungszentrum Jülich, Jülich, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Wedekind
authors.affiliation: Institute of Neuroscience and Medicine, INM-2, Forschungszentrum Jülich, Jülich, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Beer
authors.affiliation: Institute of Neuroscience and Medicine, INM-5, Forschungszentrum Jülich, Jülich, Germany.
authors.forename: Heinz H
authors.initials: HH
authors.lastname: Coenen
authors.affiliation: Institute of Neuroscience and Medicine, INM-2, Forschungszentrum Jülich, Jülich, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bauer
mesh_terms: D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism* / Q000528:radiation effects; D002940:Circadian Rhythm / Q000502:physiology* / Q000528:radiation effects; D008027:Light; D008297:Male; D010091:Oximes / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D011725:Pyridines / Q000493:pharmacokinetics; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5 / Q000378:metabolism*
chemical_list: C510950:3-(6-methylpyridin-2-ylethynyl)cyclohex-2-enone-O-methyloxime; D010091:Oximes; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5
keywords: central nervous system; chronobiology; multi-linear reference tissue model; neuroreceptor; synapse