PROTECTIVE EFFECT OF HALOPERIDOL ON OXYGEN/GLUCOSE DEPRIVATION-AND NMDA-INDUCED INJURIES ON RAT HIPPOCAMPAL SLICES AND PRIMARY NEURONS

AIM To investigate the potential neuroprotective effect of haloperidol on oxygen/glucose deprivation (OGD)- and N-methyl-D-aspartate (NMDA)-induced injuries on rat hippocampal slices in vitro and hippocampal neurons in primary culture, and the possible mechanism. METHODS OGD was performed in glucose-free artificial cerebrospinal fluid bubbled with 95% N 2 + 5% CO 2 in rat hippocampal slices. The viability of the slices was determined by measuring TTC formazan product. Hippocampal slices and primary neurons were also used to determine the toxic effect of NMDA and the protective effect of haloperidol. RESULTS OGD for 1 h significantly decreased the TTC staining of hippocampal slices. Haloperidol at 1 and 10 μmol·L -1 significantly inhibited OGD-induced decrease by 17.7% and 25% respectively, but domperidone, a D 2 dopamine receptor antagonist, did not show this effect. Dopamine did not affect the viability of normal hippocampal slices. Like OGD insult, NMDA challenge significantly decreased both the viabilities of hippocampal slices and cultured primary neurons, which were prevented by haloperidol co-treatment. CONCLUSION Haloperidol exhibited protective effect on OGD-induced injury of rat hippocampal slices and NMDA-induced injuries on both hippocampal slices and primary neurons. Its effect on OGD insult may be via mechanisms beyond dopamine-receptor blockade, but probably related to NMDA-receptor inhibition.