Gamma-aminobutyric acid neuropharmacological investigations on narcosis produced by nitrogen, argon, or nitrous oxide.
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 gamma-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.


CONCLUSIONS
We studied the effects in the rat of gamma-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.
Abraini
Jacques H
JH
*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.
Kriem
Badreddine
B
Balon
Norbert
N
Rostain
Jean-Claude
JC
Risso
Jean-Jacques
JJ
D000769:Anesthesia, Inhalation; D000818:Animals; D001128:Argon / Q000494:pharmacology*; D001418:Baclofen / Q000031:analogs & derivatives* / Q000494:pharmacology; D005442:Flumazenil / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D007276:Injections, Intraventricular; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009584:Nitrogen / Q000494:pharmacology*; D009609:Nitrous Oxide / Q000494:pharmacology*; D011724:Pyridazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D011724:Pyridazines; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; D001128:Argon; C049853:gabazine; D001418:Baclofen; D009609:Nitrous Oxide; D009584:Nitrogen; C057491:2-hydroxysaclofen