How can an inert gas counterbalance a NMDA-induced glutamate release?

1 Institut de Médecine Navale du Service de Santé des Armées, IRBA Toulon, Department of Marine and Underwater Research, UMR-MD2, Toulon Cedex 9; and ; 2 Université de la Méditerranée, Laboratoire de Physiologie et Physiopathologie en Conditions d'Oxygénation Extrêmes, UMR-MD2, Institut Jean-Roche, Faculté de Médecine Nord, Marseille Cedex 20, France Submitted 30 January 2009 ; accepted in final form 19 August 2009 Previous neurochemical studies performed in rats have revealed a decrease of striatal dopamine and glutamate induced by inert gas narcosis. We sought to establish the hypothetical role of glutamate and its main receptor, the N -methyl- D -aspartate (NMDA) receptor, in this syndrome. We aimed to counteract the nitrogen narcosis-induced glutamate and dopamine decreases by stimulating the NMDA receptor in the striatum. We used bilateral retrodialysis on awake rats, submitted to nitrogen under pressure (3 MPa). Continuous infusion of 2 mM of NMDA under normobaric conditions (0.01 MPa) ( n = 8) significantly increased extracellular average levels of glutamate, aspartate, glutamine, and asparagine by 241.8%, 292.5%, 108.3%, and 195.3%, respectively. The same infusion conducted under nitrogen at 3 MPa ( n = 6) revealed significant lower levels of these amino acids ( n = 8/6, P > 0.001). In opposition, the NMDA-induced effects on dopamine, dihydrophenylacetic acid (DOPAC), and homovanillic acid (HVA) levels were statistically not affected by the nitrogen at 3 MPa exposure ( n = 8/6, P > 0.05). Dopamine was increased by >240% on average. HVA was decreased (down to 40%), and there was no change in DOPAC levels, in both conditions. Results highlight that the NMDA receptor is not directly affected by nitrogen under pressure as indicated by the elevation in NMDA-induced dopamine release under hyperbaric nitrogen. On the other hand, the NMDA-evoked glutamate increase is counteracted by nitrogen narcosis. No improvement in motor and locomotor disturbances was observed with high striatal concentration in dopamine. Further experiments have to be done to specify why the striatal glutamate pathways, in association with the inhibition of its metabolism, only are affected by nitrogen narcosis in this study. dopamine; striatum; nitrogen narcosis; rat; anesthetic gas Address for reprint requests and other correspondence: N. Vallee, Institut de Médecine Navale du Service de Santé des Armées, IRBA Toulon, Dept. of Marine and Underwater Research, UMR-MD2, BP 20548, 83049