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.