Evidence that oxytocin exerts anxiolytic effects via oxytocin receptor expressed in serotonergic neurons in mice.
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.
Yoshida
Masahide
M
Department of Molecular and Cell Biology, Graduate School of Agricultural Science, Tohoku University, Aoba-ku, Sendai, Miyagi 981-8555, Japan.
Takayanagi
Yuki
Y
Inoue
Kiyoshi
K
Kimura
Tadashi
T
Young
Larry J
LJ
Onaka
Tatsushi
T
Nishimori
Katsuhiko
K
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001008:Anxiety Disorders / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D001426:Bacterial Proteins / Q000235:genetics; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002678:Chimera; D005260:Female; D055879:Gene Knock-In Techniques; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010121:Oxytocin / Q000378:metabolism* / Q000494:pharmacology; D011903:Raphe Nuclei / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism; D018045:Receptors, Oxytocin / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D058830:Serotonin 5-HT2 Receptor Antagonists; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014365:Tryptophan Hydroxylase / Q000378:metabolism
D014151:Anti-Anxiety Agents; D001426:Bacterial Proteins; D008164:Luminescent Proteins; D044402:Receptor, Serotonin, 5-HT2A; D018045:Receptors, Oxytocin; D058830:Serotonin 5-HT2 Receptor Antagonists; C054562:yellow fluorescent protein, Bacteria; D012701:Serotonin; D010121:Oxytocin; D014365:Tryptophan Hydroxylase