Effects of delayed treatment with nebracetam on neurotransmitters in brain regions after microsphere embolism in rats.

Abstract

1. The effects of delayed treatment with nebracetam, a novel nootropic drug, on neurotransmitters of brain regions were examined in rats with microsphere embolism-induced cerebral ischaemia. 2. Cerebral ischaemia was induced by administration of 900 microspheres (48 microns) into the internal carotid artery. The rats with stroke-like symptoms were treated p.o. with 30 mg kg-1 nebracetam twice daily. The levels of acetylcholine, dopamine, noradrenaline, 5-hydroxytryptamine (5-HT) and their metabolites in the cerebral cortex, striatum and hippocampus of animals with microsphere embolism were determined by high performance liquid chromatography (h.p.l.c.) on the 3rd and 7th days after the operation. 3. Although the microsphere embolism induced significant changes in most of the neurotransmitters and some of their metabolites in the brain regions, the delayed treatment with nebracetam partially restored only the hippocampal 5-HT and the striatal dopamine metabolite contents on the 3rd day. 4. The hippocampal in vivo 5-HT synthesis, but not the striatal dopamine synthesis, was attenuated in rats with microsphere embolism on the 3rd day, but was restored by treatment with nebracetam. In vivo striatal dopamine turnover rate of the rats with microsphere embolism was inhibited on the 3rd day irrespective of treatment with nebracetam. 5. The present study provides evidence for a possible action of nebracetam on 5-HT metabolism in the ischaemic brain.