The Differential Effects of Nitrous Oxide and Xenon on Extracellular Dopamine Levels in the Rat Nucleus Accumbens: A Microdialysis Study

Abstract

Dopamine release in the nucleus accumbens (NAC) plays a crucial role in the action of various psychotropic and addictive drugs, such as antagonists of the N-methyl-D-aspartate subtype of the glutamate. Although both nitrous oxide and xenon are N-methyl-D-aspartate receptor antagonists, they differ in their potential for producing neuropsychological toxicity; therefore, we decided to examine their effects on both spontaneous and ketamine-induced extracellular dopamine levels in the NAC. A microdialysis probe was implanted into the NAC in each of 35 rats, which were randomly assigned to one of six groups: exposure to 40% O2, exposure to 60% nitrous oxide (0.27 MAC), exposure to 43% xenon (0.27 MAC) for 60 min, and three groups exposed to either 40% O2, 60% nitrous oxide, or 43% xenon for 70 min and 80 mg/kg ketamine was given i.p. 10 min after the initiation of gas exposure. Perfusate samples were collected every 20 min, and the dopamine levels were measured using a high-performance liquid chromatography system. Nitrous oxide, but not xenon, significantly increased the dopamine level. Ketamine significantly increased the dopamine level, and this was significantly inhibited by xenon, but not by nitrous oxide. These data suggest that the difference in neuropsychological activity between nitrous oxide and xenon is partly due to their differential effects on the mesolimbic dopamine system.

Dopamine uptake dynamics are preserved under isoflurane anesthesia

“…This may appear to be in contrast to previous investigations that suggested isoflurane enhances the effect of DAT inhibitors, including cocaine [16, 22]. Those studies, however, used isoflurane mixed with 70% N 2 O, an agent that has been shown to alter DA signaling on its own [11, 21], and thus the extent to which these effects are attributable to N 2 O versus isoflurane remains unclear. Whether urethane or isoflurane alter the effects of cocaine in vivo remains an open question, however, our ex vivo results indicate that exposure to these anesthetics does not alter the action of cocaine on DA terminals and our in vivo results suggest that any changes in cocaine’s action are similar between urethane and isoflurane.…”

“…A limited number of studies have examined the effects of isoflurane on DA signaling. Unfortunately, many of these studies either administered isoflurane with N 2 O, an agent that produces changes in DA signaling on its own [11, 21], or used concentrations of isoflurane that are higher than necessary to maintain surgical level anesthesia (2–6%). For example, studies in which isoflurane was administered in combination with N 2 O indicate that extracellular DA concentrations are elevated through interactions with the DA transporter (DAT) [16, 22].…”

Effect of ketamine administration, alone and in combination with E-6837, on climbing behavior

“…A blockade of NMDARs located on GABA interneurons, when exerted by MK-801, phencyclidine, and ketamine, decreases GABAergic inhibition (Littlewood et al, 2006;Sakamoto et al, 2006;Homayoun and Moghaddam, 2007). The fact that NMDAR antagonists reduce GAD67 and parvalbumin expression, two of the main markers of GABAergic inhibitory function (Lai et al, 2014;Briones et al, 2015), would suggest an interaction between glutamatergic and dopaminergic systems.…”

Uso do óxido nitroso em pediatria

“…Another hypothesized mechanism for the neurotoxicity triggered by nitrous oxide is the interference with dopamine release mechanisms 79 (D). While these findings raise concern about the administration of nitrous oxide in combination with other NMDA antagonists, the risk of neurotoxicity should decrease when its administration is combined with other general anesthetics that exert a GABAergic effect and minimize the possible neurotoxicity of nitrous oxide 78 (D).…”