The neuroprotective effects of dextromethorphan on guinea pig-derived hippocampal slices during hypoxia

The purpose of this study was to determine whether dextromethorphan, an opioid class antitussive, prevents hypoxia-induced loss of nerve function in an in vitro hippocampal slice preparation. The evoked population spike (PS) was recorded from CA1 pyramidal cells of guinea pig-derived hippocampal slices. Hippocampal slices were superfused with O2 (95%)/CO2 (5%) gassed artificial cerebral spinal fluid (ACSF) at 37 degrees C. The PS did not recover during reoxygenation in slices that were made hypoxic for 30 min by exposure to N2 (95%)/CO2 (5%) gassed ACSF in place of oxygenated ACSF. The PS recovered during reoxygenation, following 30 min of hypoxia, in 9 of 10 slices treated with dextromethorphan (100 microM) and in 4 of 6 slices treated with D,L-2-amino-5-phosphono-valerate (AP-5) (100 microM), an NMDA receptor antagonist. The mean PS amplitudes, one hour after perfusion with oxygenated ACSF, were 42% and 51%, respectively, of the pre-hypoxia amplitude. The PS recovered during reoxygenation in all of seven slices superfused with lowered temperature ACSF (25 degrees C) during 30 min of hypoxia. The results show that dextromethorphan, like the NMDA antagonist AP-5 and lowered temperature, protected neurons from hypoxia-induced injury in the hippocampus.