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ANESTHETIC PHARMACOLOGY

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

Sachiyo Sakamoto, MD^*, Shinichi Nakao, MD, PhD^*, Munehiro Masuzawa, MD, PhD^*, Takefumi Inada, MD^*, Mervyn Maze, MBChB, FRCP, FRCA, FMedSci, Nicholas P. Franks, PhD, FMedSci, and Koh Shingu, MD, PhD^*

From the *Department of Anesthesiology, Kansai Medical University, Osaka, Japan and Magill Department of Anaesthesia, Chelsea and Westminster Hospital and Biophysics Section, The Blackett Laboratory, Imperial College of Science, Technology and Medicine, London, United Kingdom.

Address correspondence and reprint requests to Shinichi Nakao, MD, Department of Anesthesiology, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi-shi, Osaka 570-8507, Japan. Address e-mail to nakaos{at}hirakata.kmu.ac.jp.

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.

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