IS CHLORMETHIAZOLE NEUROPROTECTIVE IN EXPERIMENTAL GLOBAL CEREBRAL-ISCHEMIA - A MICRODIALYSIS AND BEHAVIORAL-STUDY

Chlormethiazole, an anticonvulsive agent, has been shown to have a pos sible neuroprotective effect against cerebral ischemia. In addition, c hlormethiazole inhibits methamphetamine-induced release of dopamine, p rotecting against this neurotransmitter's neurotoxicity. The aim of th is work was to ascertain whether, in experimental cerebral ischemia, c hlormethiazole administration attenuated the ischemia-induced rise of the extracellular concentration of aminergic neurotransmitters and whe ther it reduces ischemia-induced deficits in memory and learning; Hist ology for assessment of ischemic damage was also included. The four-ve ssel occlusion rat model was used to induce global cerebral ischemia. Aminergic neurotransmitters and their metabolites in the striatal extr acellular fluid obtained by microdialysis were assayed by high-perform ance liquid chromatography-electrochemical detection. The drug was adm inistered either IP (50 mg . kg(-1)) or directly through the dialysis probe (30 mu M) 80 min before ischemia. For the behavioral test and hi stology, the drug was given IP (100 mg . kg(-1)) 1 h postischemia. The results obtained did not demonstrate any Statistically significant ev idence that chlormethiazole has an effect on the ischemia-induced rise in extracellular dopamine and serotonin levels. There was also no var iation in metabolite levels. Behavioral measures (learning, recall) we re not changed appreciably by the treatment. We observed no significan t cell protection in the hippocampus (CA(1), CA(4)), striatum, and ent orhinal cortex in animals treated with chlormethiazole. We conclude th at, under our experimental conditions, chlormethiazole has little or n o effect on the neurochemical, neurobehavioral, and histological conse quences of global cerebral ischemia, (C) 1997 Elsevier Science Inc.