GABA(A) RECEPTOR ACTIVATION ATTENUATES EXCITOTOXICITY BUT EXACERBATESOXYGEN-GLUCOSE DEPRIVATION-INDUCED NEURONAL INJURY IN-VITRO

We examined the effects of GABA receptor stimulation on the neuronal d eath induced by exogenously added excitatory amino acids or combined o xygen-glucose deprivation in mouse cortical cell cultures. Death induc ed by exposure to NMDA, AMPA, or kainate was attenuated by addition of GABA or the GABA(A) receptor agonist muscimol, but not by the GABA(B) receptor agonist, baclofen. The antiexcitotoxic effect of GABA(A) rec eptor agonists was blocked by bicuculline or picrotoxin. In contrast, GABA or muscimol, but not baclofen, markedly increased the neuronal de ath induced by oxygen-glucose deprivation. Muscimol potentiation of ne uronal death was associated with increased glutamate efflux to the bat hing medium, and increased cellular Ca-45(2+) accumulation; it was blo cked by MK-801, but not NBQX, suggesting mediation by NMDA receptors. Bicuculline only weakly attenuated muscimol potentiation of oxygen-glu cose deprivation-induced neuronal death, probably because it itself in creased this death. Present results raise a note of caution in the pro posed use of GABA(A) receptor stimulation to limit ischemic brain dama ge in vivo.