Group II selective metabotropic glutamate receptor agonists and local cerebral glucose use in the rat

The novel mGluR agonist LY354740 and a related analogue LY379268 are select ive for mGluR2/3 receptors and are centrally active after systemic administ ration. In this study, rates of local cerebral,glucose use were measured us ing the [C-14]2-deoxyglucose autoradiographic technique to examine the func tional consequences of their systemic administration in the conscious rat. Both LY354740 (0.3, 3.0, 30 mg/kg) and LY379268 (0.1, 1.0, 10 mg/kg) produc ed dose-dependent changes in glucose use. After LY354740 (3.0mg/kg), 4 of t he 42 regions measured showed statistically significant changes from vehicl e-treated controls: red nuclei (-16%), mammillary body (-25%), anterior tha lamus (-29%), and the superficial layer of the superior colliculus (+50%). An additional 15 regions displayed significant reductions in function-relat ed glucose use (P <.05) in animals treated with LY354740 (30 mg/kg). LY3792 68 (0.1, 1.0, 10 mg/kg) produced changes in glucose metabolism in 20% of th e brain regions analyzed. Significant increases (P <.05) in glucose use wer e evident in the following: the superficial layer of the superior colliculu s (+81%), locus coeruleus (+57%), genu of the corpus callosum (+31%). cochl ear nucleus (+26%), inferior colliculus (+20%), and the molecular layer of the hippocampus (+14%). Three regions displayed significant decreases: mamm illary body (-34%), anteroventral thalamic nucleus (-28%), and the lateral habenular nucleus (-24%). These results show the important functional invol vement of the limbic system together with the participation of components o f different sensory systems in response to the activation of mGluR2 and mGl uR3 with LY354740 and LY379268.