Galantamine prevents long-lasting suppression of excitatory synaptic transmission in CA1 pyramidal neurons of soman-challenged guinea pigs

摘要

Galantamine, a drug currently approved for the treatment of Alzheimer's disease, has recently emerged as an effective pretreatment against the acute toxicity and delayed cognitive deficits induced by organophosphorus (OP) nerve agents, including soman. Since cognitive deficits can result from impaired glutamatergic transmission in the hippocampus, the present study was designed to test the hypothesis that hippocampal glutamatergic transmission declines following an acute exposure to soman and that this effect can be prevented by galantamine. To test this hypothesis, spontaneous excitatory postsynaptic currents (EPSCs) were recorded from CM pyramidal neurons in hippocampal slices obtained at 1 h, 24 h, or 6-9 days after guinea pigs were injected with: (i) 1 x LOH, soman (26.3 mu g/kg, s.c.); (ii) galantamine (8 mg/kg, i.m.) followed 30 min later by 1 x LD50 soman, (iii) galantamine (8 mg/1