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Mechanism of Action of Nitrogen Pressure in Controlling Striatal Dopamine Level of Freely Moving Rats is Changed by Recurrent Exposures to Nitrogen Narcosis

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Abstract

In rats, a single exposure to 3 MPa nitrogen induces change in motor processes, a sedative action and a decrease in dopamine release in the striatum. These changes due to a narcotic effect of nitrogen have been attributed to a decrease in glutamatergic control and the facilitation of GABAergic neurotransmission involving NMDA and GABAA receptors, respectively. After repeated exposure to nitrogen narcosis, a second exposure to 3 MPa increased dopamine levels suggesting a change in the control of the dopaminergic pathway. We investigated the role of the nigral NMDA and GABAA receptors in changes in the striatal dopamine levels. Dopamine-sensitive electrodes were implanted into the striatum under general anesthesia, together with a guide-cannula for drug injections into the SNc. Dopamine level was monitored by in vivo voltammetry. The effects of NMDA/GABAA receptor agonists (NMDA/muscimol) and antagonists (AP7/gabazine) on dopamine levels were investigated. Rats were exposed to 3 MPa nitrogen before and after five daily exposures to 1 MPa. After these exposures to nitrogen narcosis, gabazine, NMDA and AP7 had no effect on the nitrogen-induced increase in dopamine levels. By contrast, muscimol strongly enhanced the increase in dopamine level induced by nitrogen. Our findings suggest that repeated nitrogen exposure disrupted NMDA receptor function and decreased GABAergic input by modifying GABAA receptor sensitivity. These findings demonstrated a change in the mechanism of action of nitrogen at pressure.

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Abbreviations

AP7:

D-2-amino-7-phosphonoheptonoic acid

DA:

Dopamine

GABA:

Gamma-amino-butyric acid

MPa:

Megapascal (106 Pascal international pressure unit)

NMDA:

N-methyl-d-aspartate

SNc:

Substantia nigra pars compacta

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Acknowledgments

This study was supported by a research grant from the Direction Générale de l’Armement, Paris, France. PEA no. 010809/06Co024.

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Correspondence to Jean-Claude Rostain.

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Lavoute, C., Weiss, M., Risso, JJ. et al. Mechanism of Action of Nitrogen Pressure in Controlling Striatal Dopamine Level of Freely Moving Rats is Changed by Recurrent Exposures to Nitrogen Narcosis. Neurochem Res 37, 655–664 (2012). https://doi.org/10.1007/s11064-011-0657-1

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  • DOI: https://doi.org/10.1007/s11064-011-0657-1

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