A ketogenic diet modifies glutamate, gamma-aminobutyric acid and agmatine levels in the hippocampus of rats: A microdialysis study

The ketogenic diet (KD) is acknowledged as an unconventional option in the treatment of epilepsy. Several lines of investigation point to a possible role of glutamate and gamma-aminobutyric acid (GABA) as main contributors in this protective effect. Other biomolecules could also be involved in the beneficial consequence of the KD, for example, the diamine agmatine has been suggested to block imidazole and glutamate NMDA receptor and serves as an endogenous anticonvulsant in different animal models of epilepsy. In the present report, we have used microdialysis coupled to capillary electrophoresis to monitor microdialysate levels of GABA, glutamate and agmatine in the hippocampus of rats submitted to a KD for 15 days compared to rats on a normal rat chow diet. A significant increase in GABA and agmatine levels while no change in glutamate levels was observed. These results support the notion that the KD modifies different transmitters favoring inhibitory over excitatory neurotransmitters.