GRM5 and Alzheimer disease: When considered alongside the glutamatergic receptor data, the present results suggest that DCI’s neuroprotective profile in the 3×Tg-AD hippocampus arises from a dual action: a) Normalizing postsynaptic receptor expression (AMPA, NMDA, mGluR5), thereby preventing receptor-mediated excitotoxicity and b) Restoring presynaptic inhibitory tone through enhanced 2-AG production capacity, improving retrograde suppression of glutamate release.