In vivo Preclinical Molecular Imaging of repeated exposure to an NMDA antagonist and a glutaminase inhibitor as potential glutamatergic modulators

Glutamate is the principal excitatory neurotransmitter in the brain and at the base of a wide variety of neuropathologies, including epilepsy, autism, Fragile X and obsessive compulsive disorder. Glutamate has so become the target for novel drugs in treatment and in fundamental research settings. However, much remains unknown on the working mechanisms of these drugs and the effects of chronic administration on the glutamatergic system. This paper investigates the chronic effects of two glutamate modulating drugs with imaging techniques to further clarify their working mechanisms for future research opportunities. Animals were exposed to either Saline (1 mL/kg), MK-801 (0.3 mg/kg) or Ebselen (10 mg/kg) for 7 consecutive days. At the 6th injection, animals underwent a PET/CT with ABP-688 to visualize the mGluR5 receptor. After the 7th injection, animals underwent an MRS scan to visualize Glutamate and Glutamine content. Afterwards, results were verified by mGluR5 immunohistochemistry (IHC). PET/CT analysis revealed that animals receiving chronic MK-801 or Ebselen had a significant (p