EFFECTS OF OXIRACETAM ON NEUROTRANSMITTER RELEASE FROM RAT HIPPOCAMPUS SLICES AND SYNAPTOSOMES

The effects of the nootropic drug oxiracetam on the K+-evoked overflow of [H-3]D-aspartic acid ([H-3]D-ASP), ([H-3]acetylcholine ([H-3]ACh), [H-3]gamma-aminobutyric acid ([H-3]GABA), [H-3]noradrenaline ([H-3]NA) and [H-3]5-hydroxytryptamine ([H-3]5-HT) have been studied in superfused rat hippocampal slices. The overflow of [H-3]D-ASP was enhanced by low concentrations of oxiracetam (0.01-1 muM) but not by high concentrations (10-100 muM) which showed some tendency to inhibit it. Similarly, low concentrations of oxiracetam increased, although less effectively, the depolarization-evoked overflow of [H-3]ACh, whereas higher concentrations were without effect. At the concentrations active on [H-3]D-ASP and [H-3]ACh overflow oxiracetam did not affect that of [H-3]GABA, [H-3]NA or [H-3]5-HT. The oxiracetam effects present in slices could not be observed in hippocampal synaptosomes. Thus oxiracetam may selectively increase the release of glutamate and acetylcholine in hippocampus by a mechanism which appears not to be sited in the releasing nerve terminals.