Local Dosing in a 3-Mercaptopropionic Acid Chemically-Induced Epileptic Seizure Model with Microdialysis Sampling

Abstract

The focus of this research was the development of an animal model for local administration of 3-mercaptopropionic acid (3-MPA) in a chemically-induced epileptic seizure model using microdialysis sampling with simultaneous electrocorticography recording (ECoG). Local administration of 3-MPA through the microdialysis probe was employed to elicit seizures in a localized brain region. Delivery of 3-MPA to the brain and changes in amino acid and catecholamine neurotransmitters were monitored. Simultaneous ECoG recordings were made using a microdialysis probe with an internal Ag/AgCl electrode. Local administration of a convulsant is important, as many clinical cases present with focal seizures. Neurochemical and electrical activity were monitored in three separate brain regions: the striatum, hippocampus, and locus coeruleus. 3-MPA was administered through the microdialysis probe in one region, while control samples were collected in the other two. These results demonstrated that unless two brain regions were connected via efferent or afferent pathways, administration of 3-MPA in one region had no neurochemical effect in the others. In the region where 3-MPA was administered, an increase in both glutamate, the main excitatory amino acid, and GABA, the main inhibitory amino acid, was seen. In addition, an increase in both dopamine and norepinephrine was seen. A multiple dosing regimen of 3-MPA was developed where 3-MPA was administered twice. These results showed that there was an attenuation in the increase of glutamate and GABA during the second administration of 3-MPA, indicating a neuronal protective mechanism taking place to decrease the effect of the second 3-MPA administration. Seizures were not detected using during local administration of 3-MPA using the microdialysis probes with an internal Ag/AgCl electrode. This was not due to the ineffectiveness of the electrodes, as they detected seizures during systemic dosing of 3-MPA. It is possible that the number of neurons excited from the local administration of 3-MPA were so limited that the signal was too small to be detected.