Image_2_Nitrous Oxide Induces Prominent Cell Proliferation in Adult Rat Hippocampal Dentate Gyrus.TIFF ChamaaFarah BahmadHisham F. MakkawiAhmad-Kareem ChalhoubReda M. Al-ChaerElie D. BikhaziGeorge B. NahasZiad Abou-KheirWassim 2018 <p>The identification of distinct and more efficacious antidepressant treatments is highly needed. Nitrous oxide (N<sub>2</sub>O) is an N-methyl-D-aspartic acid (NMDA) antagonist that has been reported to exhibit antidepressant effects in treatment-resistant depression (TRD) patients. Yet, no studies have investigated the effects of sub-anesthetic dosages of N<sub>2</sub>O on hippocampal cell proliferation and neurogenesis in adult brain rats. In our study, adult male Sprague-Dawley rats were exposed to single or multiple exposures to mixtures of 70% N<sub>2</sub>O and 30% oxygen (O<sub>2</sub>). Sham groups were exposed to 30% O<sub>2</sub> and the control groups to atmospheric air. Hippocampal cell proliferation was assessed by bromodeoxyuridine (BrdU) incorporation, and BrdU-positive cells were counted in the dentate gyrus (DG) using confocal microscopy. Results showed that while the rates of hippocampal cell proliferation were comparable between the N<sub>2</sub>O and sham groups at day 1, levels increased by 1.4 folds at day 7 after one session exposure to N<sub>2</sub>O. Multiple N<sub>2</sub>O exposures significantly increased the rate of hippocampal cell proliferation to two folds. Therefore, sub-anesthetic doses of N<sub>2</sub>O, similar to ketamine, increase hippocampal cell proliferation, suggesting that there will ultimately be an increase in neurogenesis. Future studies should investigate added N<sub>2</sub>O exposures and their antidepressant behavioral correlates.</p>