Haloperidol reduces K(+)-evoked Ca(2+)-dependent D-[3H]aspartate release from rat hippocampal slices

Rat hippocampal slices preloaded with D-[3H]aspartate, a non metabolizable analogue of L-glutamate, were superfused with artificial CSF. Depolarization was induced by 53.5 mM K+, in the presence of Ca2+ (1.3 mM) or Mg2+ (5 mM) to determine the Ca2+ dependent release. Haloperidol added in the superfusion medium at 100 microM reduced by about 60% the Ca2+ dependent release of D-[3H]aspartate. This drug at 20 microM or 100 microM inhibited the non-activated glutamate dehydrogenase (GDH) but had no effect on GDH activated by ADP (2 mM) or leucine (5 mM). In addition no effect was observed on phosphate activated glutaminase (PAG) in the presence either of 20 mM or 5 mM phosphate. These results indicate that the effect of haloperidol is exerted on presynaptic mechanisms regulating neurotransmitter release.