Abstract
INTRODUCTION: When humans breathe compressed air or N(2)-O(2) mixtures at three to four atmospheres pressure, they will experience nitrogen narcosis that may possibly lead to a diving accident, but the underlying mechanisms remain unclear. METHODS: Mice were exposed to 1.6 MPa breathing a N(2)-O(2) mixture adjusted to deliver an inspired PO(2) of 32-42 kPa. The electroencephalogram (EEG) and forced swimming test were used to evaluate the narcotic effect of nitrogen. Neuronal activity was observed via c-Fos expression in cortex and hippocampus tissue after decompressing to the surface. To further investigate underlying molecular mechanisms, we incubated cultured hippocampal neurons with various NMDA concentrations, and measured expression of NMDA receptors and its down-stream signal with or without 1.6 MPa N(2)-O(2) exposure. RESULTS: Both the frequency of the EEG and the drowning time using the forced swimming test were significantly decreased during exposure to 1.6 MPa N(2)-O(2) (P < 0.001). Additionally, in cultured hippocampal neurons, the increased levels of phosphorylated NR2B and cAMP-response element binding protein (CREB) induced by NMDA stimulation were significantly inhibited by exposure to 1.6 MPa N(2)-O(2). CONCLUSIONS: Our findings indicated that NR2B-containing NMDA receptors were inhibited during nitrogen narcosis.