The group 2 metabotropic glutamate receptor agonist LY379268 rescues neuronal, neurochemical and motor abnormalities in R6/2 Huntington's disease mice

► The mGluR2/3 agonist LY379268 extended lifespan. ► LY379268 normalized open field motor parameters for much of the R6/2 lifespan. ► LY379268 rescued cortical and striatal neuron loss. ► LY379268 normalized substance P-containing striatal projection neuron neurochemistry. ► The R6/2 phenotype is accelerated in males, and LY379268 benefit greater in males.