HALOPERIDOL REDUCES K-EVOKED CA2+-DEPENDENT D-[H-3]ASPARTATE RELEASE FROM RAT HIPPOCAMPAL SLICES()

Rat hippocampal slices preloaded with D-[H-3]aspartate, a non metaboli zable analogue of L-glutamate, were superfused with artificial CSF. De polarization was induced by 53.5 mM K+, in the presence of Ca2+ (1.3 m M) or Mg2+ (5 mM) to determine the Ca2+ dependent release. Haloperidol added in the superfusion medium at 100 mu M reduced by about 60% the Ca2+ dependent release of D-[H-3]aspartate. This drug at 20 mu M or 10 0 mu M inhibited the non-activated glutamate dehydrogenase (GDH) but h ad no effect on GDH activated by ADP (2 mM) or leucine (5 mM). In addi tion no effect was observed on phosphate activated glutaminase (PAG) i n the presence either of 20 mM or 5 mM phosphate. These results indica te that the effect of haloperidol is exerted on presynaptic mechanisms regulating neurotransmitter release.