Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada; Department of Psychology, University of British Columbia, Vancouver, BC, Canada.
Graduate Program in Neuroscience, University of British Columbia, Vancouver, BC, Canada.
Horm Behav. 2020 Jun;122:104734. doi: 10.1016/j.yhbeh.2020.104734. Epub 2020 Mar 21.
Oxytocin regulates social behaviours, pair bonding and hippocampal neurogenesis but most studies have used adult males. Our study investigated the effects of oxytocin on social investigation and adult hippocampal neurogenesis in male and female rats. Oxytocin has poor penetration of the blood-brain barrier, therefore we tested a nanoparticle drug, TRIOZAN™ (Ovensa Inc.), which permits greater blood-brain-barrier penetration. Adult male and female rats were injected daily (i.p.) for 10 days with either: oxytocin in PBS (0.5 or 1.0 mg/kg), oxytocin in TRIOZAN™ (0.5 or 1.0 mg/kg), or vehicle (PBS) and tested for social investigation. Oxytocin decreased body mass and increased social investigation and number of oxytocin-immunoreactive cells in the supraoptic nucleus (SON) of the hypothalamus in male rats only. In both sexes, oxytocin decreased the number of immature neurons (doublecortin+ cells) in the ventral hippocampus and reduced plasma 17β-estradiol levels in a dose- and delivery-dependent way. Oxytocin in TRIOZAN™ reduced "sedation" observed post-injection and increased certain central effects (oxytocin levels in the hypothalamus and neurogenesis in the ventral hippocampus) relative to oxytocin in PBS, indicating that the nanoparticle may be used as an alternative brain delivery system. We showed that oxytocin has sex-specific effects on social investigation, body mass, "sedation", and the oxytocin system. In contrast, similar effects were observed in both sexes in neurogenesis and plasma 17β-estradiol. Our work suggests that sex differences in oxytocin regulation of brain endpoints is region-specific (hypothalamus versus hippocampus) and that oxytocin does not promote social investigation in females.
催产素调节社会行为、伴侣结合和海马神经发生，但大多数研究都使用成年雄性动物。我们的研究调查了催产素对雄性和雌性大鼠社会探索和成年海马神经发生的影响。催产素很难穿透血脑屏障，因此我们测试了一种纳米颗粒药物 TRIOZAN™（Ovensa Inc.），它可以增加血脑屏障的穿透性。成年雄性和雌性大鼠每天（ip）注射：PBS 中的催产素（0.5 或 1.0mg/kg）、TRIOZAN™ 中的催产素（0.5 或 1.0mg/kg）或载体（PBS），并进行社会探索测试。催产素降低了雄性大鼠的体重，增加了社会探索和下丘脑视上核（SON）中催产素免疫反应细胞的数量。在两性中，催产素以剂量和传递依赖的方式减少了腹侧海马中的未成熟神经元（双皮质素+细胞）的数量，并降低了血浆 17β-雌二醇水平。TRIOZAN™ 中的催产素减少了注射后观察到的“镇静”，并增加了某些中枢效应（下丘脑的催产素水平和腹侧海马的神经发生），与 PBS 中的催产素相比，这表明纳米颗粒可用作替代大脑传递系统。我们表明，催产素对社会探索、体重、“镇静”和催产素系统具有性别特异性影响。相比之下，在神经发生和血浆 17β-雌二醇方面，两性中观察到相似的影响。我们的工作表明，催产素对大脑终点的调节存在性别差异，是特定于区域的（下丘脑与海马），并且催产素不会促进雌性的社会探索。
