A study of the role of serotonin in the anxiolytic effect of nitrous oxide in rodents

Dimitris E Emmanouil,Z Papadopoulou-Daifoti,Philip T Hagihara,Daniel G Quock,Raymond M Quock

doi:10.1016/j.pbb.2006.05.016

Abstract

Rationale In earlier studies, we have shown that nitrous oxide (N 2O)-induced behavioral effects in rats and mice are mediated by benzodiazepine receptors. Objectives This two-part study was conducted in order to investigate the possible role of serotonin (5-HT) in the behavioral effects of N 2O by clarifying its effects on regional brain concentrations of 5-HT and assessing the influence of 5-HT antagonist and reuptake inhibiting drugs on the anxiolytic-like behavioral effect of N 2O. Methods In experiment A, male, 150–200 g Sprague–Dawley rats were killed following a 15-min exposure to room air or 70% N 2O. The frontal cortex, hippocampus, corpus striatum and hypothalamus were dissected out and analyzed by HPLC with electrochemical detection for content of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA); dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) were also measured. In experiment B, male 18–22 g NIH Swiss mice were pretreated with the 5-HT 2 antagonist cinanserin, the 5-HT 3 antagonist LY-278,584, the 5-HT reuptake inhibitor fluoxetine or saline and tested in the light/dark exploration test under 70% N 2O 30 min after pretreatment. Results In experiment A, N 2O produced differential effects on 5-HT neurons in distinct brain areas. There was increased 5-HT turnover in the hypothalamus, decreased turnover in the frontal cortex but no changes in either hippocampus or corpus striatum. By comparison, dopamine turnover in these brain regions was unaltered by N 2O exposure. In experiment B, pretreatment with neither cinanserin, LY-278,584 nor fluoxetine had any appreciable effect on the N 2O-induced increase in time spent in the light compartment. Only cinanserin significantly reduced the N 2O-induced increase in transitions. Conclusions While neurochemical results suggest an effect of N 2O on brain 5-HT function, there was no effect of 5-HT 2 or 5-HT 3 antagonists or 5-HT reuptake inhibitor on N 2O-induced anxiolytic-like behavior.

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