Nitrous oxide and xenon prevent amphetamine-induced carrier-mediated dopamine release in a memantine-like fashion and protect against behavioral sensitization

Biol Psychiatry. 2006 Jul 1;60(1):49-57. doi: 10.1016/j.biopsych.2005.10.007. Epub 2006 Jan 19.


Background: Amphetamine administration induces stimulation-independent dopamine release in the nucleus accumbens (NAcc) through reverse dopamine transport, a critical neurochemical event involved in its psychostimulant action, and furthermore decreases stimulation-dependent vesicular dopamine release. These effects may involve possible indirect glutamatergic mechanisms.

Methods: We investigated the effects of nitrous oxide and xenon, which possess antagonistic action at the N-methyl-D-aspartate (NMDA) receptor, on brain slices ex vivo on amphetamine-induced changes in carrier-mediated and KCl-evoked dopamine release in the NAcc, and in vivo on amphetamine-induced locomotor sensitization.

Results: Like the low-affinity NMDA receptor antagonist memantine, but not the prototypical compound MK-801, nitrous oxide and xenon at appropriate concentrations blocked both the increase in carrier-mediated dopamine release and locomotor sensitization produced by amphetamine.

Conclusions: In contrast to what has generally been found using prototypical NMDA receptor antagonists, these data regarding the effect of memantine, nitrous oxide, and xenon support the hypothesis that activation of certain NMDA receptors (possibly those containing the NR1a/NR2D subunit) in the NAcc is involved in the amphetamine-induced increase in carrier-mediated dopamine release and the development of behavioral sensitization to amphetamine. Nitrous oxide, xenon, and memantine may be of therapeutic interest for treating drug dependence.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphetamine / administration & dosage*
  • Animals
  • Behavior, Animal / drug effects
  • Central Nervous System Stimulants / administration & dosage*
  • Dizocilpine Maleate / pharmacology
  • Dopamine / metabolism*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Excitatory Amino Acid Antagonists / pharmacology*
  • In Vitro Techniques
  • Male
  • Memantine / pharmacology*
  • Motor Activity / drug effects*
  • Nitrous Oxide / pharmacology*
  • Nucleus Accumbens / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Xenon / pharmacology*


  • Central Nervous System Stimulants
  • Excitatory Amino Acid Antagonists
  • Xenon
  • Dizocilpine Maleate
  • Amphetamine
  • Nitrous Oxide
  • Dopamine
  • Memantine