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

Abstract

Summary The metabotrophic subtype 5 glutamate receptor ( mG luR5) plays a critical role in synaptic plasticity besides its involvement in numerous neurological disorders, such as depression. As mG luR5 availability in humans is altered in sleep deprivation, we hypothesized that mG luR5 availability underlies a circadian variation. To investigate whether mG luR5 underlies potential circadian changes we measured its density in a randomized fashion at six different daytimes in 11 adult Sprague–Dawley rats. mG luR5 density was quantified by positron emission tomography ( PET ) using the radioactive ligand [ 11 C] ABP 688. [ 11 C] ABP 688 uptake was quantified in nine regions of interest with a reference tissue model. Significant differences in the binding potential ( BP ND ) and therefore mG luR5 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 BP ND between 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 mG luR5 availability is increased during the light‐on, or sleep phase, of rodents by approximately 10%. Given that altered mG luR5 densities play a role in psychiatric disorders, further investigation is warranted to evaluate their circadian involvement in mood changes in humans.