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ANESTHETIC PHARMACOLOGY

Gamma-Aminobutyric Acid Neuropharmacological Investigations on Narcosis Produced by Nitrogen, Argon, or Nitrous Oxide

Jacques H. Abraini^*, Badreddine Kriem, Norbert Balon, Jean-Claude Rostain, and Jean-Jacques Risso^,

*UMR CNRS 6551 Mort Neuronale, Neuroprotection, Neurotransmission, Université de Caen, Centre Cyceron; EMI INSERM 0014, Université Henri Poincaré Nancy 1; UPRES EA3280, Université de la Méditerranée, Marseille; and Institut de Médecine Navale du Service de Santé des Armées (IMNSSA), Toulon, France

Address correspondence and reprint requests to Dr. Jacques H. Abraini, Université de Caen, UMR CNRS 6551, Centre Cyceron, BP 5229, Boulevard Henri Becquerel, 14074 Caen Cedex, France. Address e-mail to abraini{at}neuro.unicaen.fr

Inhaled anesthetics, including the gaseous anesthetics nitrous oxide and xenon, are thought to act by interacting directly with ion-channel receptors. In contrast, little is known about the mechanism of action of inert gases that show only narcotic potency at high pressures, such as nitrogen or argon. In the present study, we investigated the effects of selective -aminobutyric acid (GABA) receptor antagonists on narcosis produced by nitrogen, argon, and nitrous oxide. Pretreatment with the competitive GABA_A receptor antagonist gabazine (0.2 nmol) but not the GABA_B receptor antagonist 2-hydroxysaclofen (10 nmol) increased the nitrogen and argon threshold pressure for loss-of-righting-reflex (P < 0.005) but had no effect on nitrous oxide narcosis. Pretreatment with the GABA_A benzodiazepine receptor antagonist flumazenil (5 nmol) also increased the narcosis threshold pressure of argon (P < 0.025). Given that neither 2-hydroxysaclofen, gabazine, nor flumazenil at the doses used induced hyperexcitability, our results support a selective antagonism by gabazine and flumazenil of the narcotic action of nitrogen and argon. Some mechanisms of nitrogen and argon narcotic action might be similar to those of clinical inhaled anesthetics.

IMPLICATIONS: We studied the effects in the rat of -aminobutyric acid (GABA) receptor antagonists on narcosis induced by nitrogen and argon that act only at high pressures. Our results show that the GABA _A receptor may play a significant role, suggesting that some mechanisms might be similar to those of clinical inhaled anesthetics.