EFFECTS OF DELAYED TREATMENT WITH NEBRACETAM ON NEUROTRANSMITTERS IN BRAIN-REGIONS AFTER MICROSPHERE EMBOLISM IN RATS

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 mu m) into the internal carotid artery. The rats with stroke-like symptoms were treat ed p.o. with 30 mg kg(-1) nebracetam twice daily. The levels of acetyl choline, dopamine, noradrenaline, 5-hydroxytryptamine (5-HT) and their metabolites in the cerebral cortex, striatum and hippocampus of anima ls with microsphere embolism were determined by high performance liqui d chromatography (h.p.l.c.) on the 3rd and 7th days after the operatio n. 3 Although the microsphere embolism induced significant changes in most of the neurotransmitters and some of their metabolites in the bra in regions, the delayed treatment with nebracetam partially restored o nly 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 n ebracetam. 5 The present study provides evidence for a possible action of nebracetam on 5-HT metabolism in the ischaemic brain.