Circadian variation of metabotropic glutamate receptor 5 availability in the rat brain

Abstract

The metabotropic subtype 5 glutamate receptor (mGluR5) plays a critical role in synaptic plasticity besides its involvement in numerous neurological disorders like 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 6 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 BPND between 7am (start of light-on phase) and 3pm (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 about 10%. Given that altered mGluR5 densities play a role in psychiatric disorders further investigation are warranted to evaluate their circadian involvement in mood changes in humans.