Yoshida Masahide, Takayanagi Yuki, Inoue Kiyoshi, Kimura Tadashi, Young Larry J, Onaka Tatsushi, Nishimori Katsuhiko
Department of Molecular and Cell Biology, Graduate School of Agricultural Science, Tohoku University, Aoba-ku, Sendai, Miyagi 981-8555, Japan.
J Neurosci. 2009 Feb 18;29(7):2259-71. doi: 10.1523/JNEUROSCI.5593-08.2009.
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.
催产素受体与生殖生理以及社会和情感行为的调节有关。催产素受体调节社会和情感行为的神经化学机制仍然难以捉摸，部分原因是缺乏用于细胞定位的灵敏且选择性的抗体。为了更精确地表征大脑中表达催产素受体的神经元，我们构建了一种催产素受体报告基因小鼠，其中催产素受体基因的一部分被金星cDNA（黄色荧光蛋白的一种变体）取代。对金星表达的检测显示，在中缝核中，约一半的色氨酸羟化酶免疫反应性神经元对金星呈阳性，这表明催产素在调节血清素释放方面具有潜在作用。输注催产素促进了中缝正中核内血清素的释放，并减少了焦虑相关行为。输注5-HT(2A/2C)受体拮抗剂可阻断催产素的抗焦虑作用，这表明血清素能神经元中催产素受体的激活介导了催产素的抗焦虑作用。这是首次证明催产素可能通过直接激活中缝核血清素能神经元中表达的催产素受体来调节血清素释放并发挥抗焦虑作用。这些结果对于自闭症和抑郁症等精神疾病也具有重要意义，在这些疾病中，催产素和血清素系统均与之相关。
