Hypoxic tolerance induction by a neurotoxin, 3-nitropropionic acid, in gerbil hippocampal slice model

Recently hypoxic tolerance by chemical preconditioning with the neurotoxin 3-nitropropionic acid (3-NPA), chemical inhibition of oxidative phosphorylation, was reported in rats. In this study, we determined the subclinical dose in gerbils intoxicated with 3-NPA (experiment-1) and investigated whether the tolerance phenomenon similar to chemical preconditioning in rats against hypoxia can be observed in gerbil hippocampal slices (experiment-2). At 3 hours prior to slice preparation, experimental animals were given a single intraperitoneal injection of 3-NPA at a dose of 4 mg/kg which was determined by clinical signs and morphological findings in 3-NPA-intoxicated gerbils in experiment-1. An in vitro gerbil hippocampal slice model was used to study the delay to hypoxic depolarization (HD) during hypoxia and the recovery of field excitatory postsynapic potential (fEPSP) after hypoxia. The delay to HD during hypoxia was significantly prolonged in preconditioned group (203.2 ± 78.0 sec; mean ± SD) compared to control group (84.5 ± 34.4 sec) (p