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.