Evidence That Oxytocin Exerts Anxiolytic Effects via Oxytocin Receptor Expressed in Serotonergic Neurons in Mice

• Type of Material: Article
• Authors: Masahide Yoshida, Tohoku University; Yuki Takayanagi, Jichi Medical University; Kiyoshi Inoue, Emory University; Tadashi Kimura, Osaka University; Larry Young, Emory University; Tatsushi Onaka, Jichi Medical University; Katsuhiko Nishimori, Tohoku University
• Language: English
• Date: 2009-02-18
• Publisher: Lippincott, Williams & Wilkins
• Publication Version: Final Published Version
• Copyright Statement: Copyright © 2009 Society for Neuroscience.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1523/JNEUROSCI.5593-08.2009
• Title of Journal or Parent Work: Journal of Neuroscience Nursing
• ISSN: 0888-0395
• Volume: 29
• Issue: 7
• Start Page: 2259
• End Page: 2271
• Grant/Funding Information: The contributions of L.J.Y. were supported by National Institute of Mental Health Grant MH64692; and National Science Foundation Grant IBN-9876754.; This work was supported by Ministry of Education, Culture, Sports, Science, and Technology of Japan Grants 20790194 (Y.T.) and 20590237 (T.O.); and Japan Society for the Promotion of Science Grants 17005041 (M.Y.), 20020023 (T.O.), and 18380076 (K.N.).
• Keywords: Neurosciences & Neurology; NORADRENALINE RELEASE; oxytocin; serotonin; SOCIAL RECOGNITION; autism; dopamine; Neurosciences; BRAIN OXYTOCIN; AGGRESSIVE-BEHAVIOR; MEDIAL AMYGDALA; GAMMA-AMINOBUTYRIC-ACID; RAT SUPRAOPTIC NUCLEUS; ANXIETY-RELATED BEHAVIOR; NEUROPSYCHIATRIC DISORDERS; Life Sciences & Biomedicine; DEFICIENT MICE; depression; Science & Technology; anxiety-related behavior
• Research Categories: Biology, Cell; Biology, Physiology; Biology, Neuroscience

Abstract

The oxytocin receptor has been implicated in the regulation of reproductive physiology as well as social and emotional behaviors. The neurochemical mechanisms by which oxytocin receptor modulates social and emotional behavior remains elusive, in part because of a lack of sensitive and selective antibodies for cellular localization. To more precisely characterize oxytocin receptor-expressing neurons within the brain, we generated an oxytocin receptor-reporter mouse in which part of the oxytocin receptor gene was replaced with Venus cDNA (a variant of yellow fluorescent protein). Examination of the Venus expression revealed that, in the raphe nuclei, about one-half of tryptophan hydroxylase-immunoreactive neurons were positive for Venus, suggesting a potential role for oxytocin in the modulation of serotonin release. Oxytocin infusion facilitated serotonin release within the median raphe nucleus and reduced anxiety-related behavior. Infusion of a 5-HT 2A/2C receptor antagonist blocked the anxiolytic effect of oxytocin, suggesting that oxytocin receptor activation in serotonergic neurons mediates the anxiolytic effects of oxytocin. This is the first demonstration that oxytocin may regulate serotonin release and exert anxiolytic effects via direct activation of oxytocin receptor expressed in serotonergic neurons of the raphe nuclei. These results also have important implications for psychiatric disorders such as autism and depression in which both the oxytocin and serotonin systems have been implicated.