RELEASE OF DOPAMINE, GABA AND EAA IN RATS DURING INTRASTRIATAL PERFUSION WITH KAINIC ACID, NMDA AND SOMAN - A COMPARATIVE MICRODIALYSIS STUDY

There is an increasing amount of experimental evidence that excitatory amino acids (EAAs) are involved in the brain lesions observed after s evere intoxication with the highly toxic organophosphorus compound som an. This study was undertaken to compare the acute actions of soman, a nd the glutamatergic receptor agonists kainic acid and N-methyl-D-aspa rtate (NMDA) on striatal release of dopamine and amino acids. The neur otoxic compounds were administered in high (10 mM) concentrations by u nilateral intrastriatal microdialysis perfusion in freely moving rats. During the microdialysis the animals were observed for toxic signs re lated to convulsion. The glial fibrillary acidic protein (GFAP) was mo nitored as a marker of neurotoxicity in parts of prefrontal cortex, hi ppocampus, striatum and cerebellum. Acetylcholinesterase (AChE) inhibi tion in six brain regions was measured after soman perfusion in order to assess its cerebral distribution. We found that soman perfusion ind uced a major release of dopamine, GABA and aspartate in the striatum. Kainic acid also induced a release of dopamine and aspartate. NMDA was not as potent an inducer of striatal neurotransmitter release as soma n and kainic acid. Soman and kainic acid perfusion produced convulsive behaviour in the rats. The main neurochemical event in the striatum d uring soman-and kainate-induced convulsions is the release of dopamine . We suggest that this major dopamine release might be as important as an increase in EAA in the cascade of pathological events leading to t he brain damage in the striatum observed after soman intoxication.