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

Background. Amphetamine administration induces stimulation-independent dopainine release in the nucleus accumbens (NAcc) through reverse dopamine transport, a critical neurochemical event involved in its psycbostimulant action, and, furthermore decreases stimulation-dependent vesicular dopamine release. These effects may involve possible indirect glutamateigic mechanisms. Methods: We investigated the effiects of nitrous oxide and xenon, which possess antagonistic action at the N-methyl-D-aspartate (NMDA) receptor, on brain slices ex vivo on aniphetamine-induced changes in carrier-mediated and KCI-evoked dopamine release in the NAcc, and in vivo on ampbetamine-induced locomotor sensitization Results: Like the low-affininity 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 qf memantine, nitrous oxide, and xenon support the hypothesis that activation qf certain NMDA receptors (possibly those qf containing the NR1a/NR2D subunit) in the NAcc is involved in the ampbetamine-induced increase in carrier-mediated dopamine release and the development qf behavioral sensitization to amphetamine. Nitrous oxide, xenon, and memantine may be of therapeutic interest for treating drug dependence.