European Journal of Pharmaceutical Sciences 2014-06-16

Correlation of 3-mercaptopropionic acid induced seizures and changes in striatal neurotransmitters monitored by microdialysis.

Eric W Crick, Ivan Osorio, Mark Frei, Andrew P Mayer, Craig E Lunte

Index: Eur. J. Pharm. Sci. 57 , 25-33, (2014)

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Abstract

The goal of this study was to use a status epilepticus steady-state chemical model in rats using the convulsant, 3-mercaptopropionic acid (3-MPA), and to compare the changes in striatal neurotransmission on a slow (5min) and fast (60s) timescale. In vivo microdialysis was combined with electrophysiological methods in order to provide a complete evaluation of the dynamics of the results obtained.To compare the effects of a steady-state chemical model pof status epilepticus on striatal amino-acid and amine neurotransmitters contents, as measured via in vivo microdialysis combined with electrophysiological methods. Measurements were performed on samples collected every 60s and every 5min. "Fast" (60s) and "slow" (5min) sampling timescales were selected, to gain more insight into the dynamics of GABA synthesis inhibition and of its effects on other neurotransmitters and on cortical electrical activity.3-MPA was administered in the form of an intra-venous load (60mg/kg) followed by a constant infusion (50mg/kg/min) for min. Microdialysis samples were collected from the striatum at intervals of 5min and 60s and analyzed for biogenic amine and amino acid neurotransmitters. ECoG activity was monitored via screws placed over the cortex.In the 5min samples, glutamate (Glu) increased and γ-aminobutyric acid (GABA) decreased monotonically while changes in dopamine (DA) concentration were bimodal. In the sixty second samples, Glu changes were bimodal, a feature that was not apparent with the 5min samples. ECoG activity was indicative of status epilepticus.This study describes the combination of in vivo microdialysis with electrophysiology to monitor the effect of 3-MPA on neurotransmission in the brain. This led to a better understanding of the chemical changes in the striatum due to the applied 3-MPA chemical model of status epilepticus.Copyright © 2014 Elsevier B.V. All rights reserved.