Genetically epilepsy-prone rats have increased brain regional activity of an enzyme which liberates glutamate from N-acetyl-aspartyl-glutamate.

N-Acetylated-alpha-linked acidic dipeptidase (NAALADase) is a membrane-bound peptidase which hydrolyzes the endogenous neuropeptide N-acetylaspartylglutamate (NAAG) to N-acetylaspartate (NAA) and the excitatory amino acid, glutamate (Glu). Although there is evidence that NAAG might be a neurotransmitter, this dipeptide could also function as a precursor form of Glu, which is liberated by the dipeptidase. We found that the activity of this NAAG hydrolyzing enzyme in genetically epilepsy-prone rats was 11-26% greater than control in brain regions, including the amygdala, hippocampus and cerebellum, as well as the pyriform, entorhinal and frontal cortices. This is consistent with possible increased availability of Glu in certain CNS synapses in these rats, which are reported to have increased susceptibility to audiogenically, electrically and chemically induced convulsions.