Argon prevents the development of locomotor sensitization to amphetamine and amphetamine-induced changes in mu opioid receptor in the nucleus accumbens.

Hélène N David,Géraldine Poisnel,Jean-Éric Blatteau,Nicolas Vallée,Jean-Jacques Risso,Martine Dhilly,Mickael Degoulet,Jacques H Abraini,Marc Lemaire,Cédric Meckler,Danièle Debruyne

doi:10.1186/s13618-014-0021-z

Abstract

Systemic administration of γ-amino-butyric acid type A (GABA-A) and benzodiazepine receptor agonists has been reported to block the development of locomotor sensitization to amphetamine. Here, we investigated whether the non-anesthetic noble gas argon, shown to possess agonistic properties at these receptors, may block the acquisition of amphetamine-induced locomotor sensitization and mu opioid receptor activation in the nucleus accumbens. Rats were pretreated with saline solution or amphetamine (1 mg/kg) from day 1 to day 3 and then exposed, immediately after injection of amphetamine, to medicinal air or argon at 75 vol% (with the remainder being oxygen). After a 3-day period of withdrawal, rats were challenged with amphetamine on day 7. Rats pretreated with amphetamine and argon had lower locomotor activity (U = 5, P < 0.005) and mu opioid receptor activity in the nucleus accumbens (U = 0, P < 0.001) than rats pretreated with amphetamine and air. In contrast, argon had effect on locomotor and mu receptor activity neither in rats pretreated with saline and challenged with amphetamine (acute amphetamine) nor in rats pretreated and challenged with saline solution (controls). These results indicate that argon inhibits the development of both locomotor sensitization and mu opioid receptor activation induced by repeated administration of amphetamine.

Highlights

Over the past 10 years, a series of in vitro and in vivo studies has demonstrated the organoprotective and therapeutic potential of the inert gases xenon, nitrous oxide, and argon [1,2,3,4,5,6,7,8,9,10,11,12,13]
When challenged with amphetamine, rats pretreated with saline solution and argon had locomotor activity that was not different from that displayed by rats pretreated with saline solution and air (U = 20, n.s.)
We found that argon further blocked the increase in mu receptor activity induced by repeated administration of amphetamine, but had effect neither on the increase in mu receptor activity induced by acute amphetamine nor on basal mu receptor activity in the nucleus accumbens

Summary

Introduction

Over the past 10 years, a series of in vitro and in vivo studies has demonstrated the organoprotective and therapeutic potential of the inert gases xenon, nitrous oxide, and argon [1,2,3,4,5,6,7,8,9,10,11,12,13]. In line with their antagonistic action at the N-methyl-D-aspartate (NMDA) glutamate receptor and nicotinic acetylcholine (nACh) receptor [14,15,16,17,18,19], xenon and nitrous oxide at subanesthetic doses have been shown to block the development of locomotor sensitization to amphetamine [20], which is characterized by an enhanced locomotor response to an amphetamine challenge in rats pretreated with repeated.

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Conclusion