Neurochemistry of Pressure‐Induced Nitrogen and Metabolically Inert Gas Narcosis in the Central Nervous System

Abstract

Gases that are not metabolized by the organism are thus chemically inactive under normal conditions. Such gases include the "noble gases" of the Periodic Table as well as hydrogen and nitrogen. At increasing pressure, nitrogen induces narcosis at 4 absolute atmospheres (ATAs) and more in humans and at 11 ATA and more in rats. Electrophysiological and neuropharmacological studies suggest that the striatum is a target of nitrogen narcosis. Glutamate and dopamine release from the striatum in rats are decreased by exposure to nitrogen at a pressure of 31 ATA (75% of the anesthetic threshold). Striatal dopamine levels decrease during exposure to compressed argon, an inert gas more narcotic than nitrogen, or to nitrous oxide, an anesthetic gas. Inversely, striatal dopamine levels increase during exposure to compressed helium, an inert gas with a very low narcotic potency. Exposure to nitrogen at high pressure does not change N-methyl-d-aspartate (NMDA) glutamate receptor activities in Substantia Nigra compacta and striatum but enhances gama amino butyric acidA (GABAA) receptor activities in Substantia Nigra compacta. The decrease in striatal dopamine levels in response to hyperbaric nitrogen exposure is suppressed by recurrent exposure to nitrogen narcosis, and dopamine levels increase after four or five exposures. This change, the lack of improvement of motor disturbances, the desensitization of GABAA receptors on dopamine cells during recurrent exposures and the long-lasting decrease of glutamate coupled with the higher sensitivity of NMDA receptors, suggest a nitrogen toxicity induced by repetitive exposures to narcosis. These differential changes in different neurotransmitter receptors would support the binding protein theory. © 2016 American Physiological Society. Compr Physiol 6:1579-1590, 2016.

Dopamine-dependent biphasic behaviour under ‘deep diving’ conditions in Caenorhabditis elegans

“…We tested both WT and dopamine mutant strains under compressed air, oxygen and nitrogen. We found that WT animals respond to high pressure in air and nitrogen in a biphasic curve that was similarly reported for rats [29] and resembles human behaviour in nitrogen narcosis [4,33]. The animals responded to increased pressure by first increasing their locomotion speed.…”

Inert gas narcosis in scuba diving, different gases different reactions

“…Pressure-dependent conformational changes occur due to gas-protein binding, particularly at N-methyl-d-aspartate (NMDA) and GABA A (Gamma amino butyric acid a) receptors in the substantia nigra pars compacta (Rostain et al 2011;Rostain and Lavoute 2016), which further supports the protein-binding theory of narcosis. Other pathways are likely involved in the nitrogen narcosis effects, such as reduced release of glutamate and other amino acids, which partially explain the depletion in extracellular concentrations of dopamine (Vallee et al 2009a, b).…”

Going to Extremes of Lung Physiology–Deep Breath-Hold Diving

“…In 1935, Behnke first suggested that nitrogen gas might have been the mediator of the observed behavior, by utilizing different breathing gas mixtures in their experiments (Behnke et al, 1935;Grover and Grover, 2014). Nitrogen narcosis can impede cognitive functions and physical performance from depths as low as 10 m, and will be apparent around 30-40 m depth (Rostain and Lavoute, 2016). Symptoms include spatial and temporal disorientation, memory impairments, euphoria, hallucinations, mood changes, impaired neuromuscular coordination, psychomotor and intellectual decrements and unconsciousness (Rostain et al, 2011;Rostain and Lavoute, 2016;Jain, 2017).…”