Increased brain and plasma oxytocin after nasal and peripheral administration in rats and mice

Increased brain and plasma oxytocin after nasal and peripheral administration in rats and mice
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DOI:
10.1016/j.psyneuen.2013.03.003
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发表时间:
2013-10-01
影响因子:
3.7
通讯作者:
Landgraf, Rainer
Landgraf, Rainer
中科院分区:
医学2区
文献类型:
--
作者:
Neumann, Inga D.;Maloumby, Rodrigue;Landgraf, Rainer

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通过鼻内施用合成催产素(OXT)来改善人类社会情感行为的可能性引起了越来越多的关注,但迄今为止尚未证明其被大脑吸收。在这里,我们对大鼠和小鼠的背侧海马和杏仁核进行同步微透析,并结合颈静脉采血,研究鼻腔给药后脑细胞外液和血浆中神经肽的动态。研究发现,海马和杏仁核的微透析液中 OXT 均有所增加,峰值水平出现在鼻腔给药后 30-60 分钟。尽管血浆中 OXT 浓度的时间分布相似,但根据体外恢复数据计算得出,外周 OXT 不太可能对透析液 OXT 产生影响,这表明存在中枢转运途径。此外,腹腔内给予相同量的合成OXT会在治疗后的前30分钟内导致脑透析液和血浆中的水平迅速达到峰值,并随后恢复到基线。虽然中枢运输的精确途径仍有待阐明,但我们的数据提供了第一个证据,表明经鼻施用的 OXT 确实到达了行为相关的大脑区域,并且这种吸收与血浆 OXT 的变化是平行的。 (C) 2013 Elsevier Ltd. 保留所有权利。
The possibility to improve socio-emotional behaviors in humans by intranasal administration of synthetic oxytocin (OXT) attracts increasing attention, but its uptake into the brain has never been demonstrated so far. Here we used simultaneous microdialysis in both the dorsal hippocampus and amygdala of rats and mice in combination with concomitant blood sampling from the jugular vein to study the dynamics of the neuropeptide in brain extracellular fluid and plasma after its nasal administration. OXT was found to be increased in microdialysates from both the hippocampus and amygdala with peak levels occurring 30-60 min after nasal administration. Despite a similar temporal profile of OXT concentrations in plasma, peripheral OXT is unlikely to contribute to dialysate OXT as calculated from in vitro recovery data, indicating a central route of transport. Moreover, intraperitoneal administration of synthetic OXT in identical amounts caused rapid peak levels in brain dialysates and plasma during the first 30 min after treatment and a subsequent return toward baseline. While the precise route(s) of central transport remain to be elucidated, our data provide the first evidence that nasally applied OXT indeed reaches behaviorally relevant brain areas, and this uptake is paralleled by changes in plasma OXT. (C) 2013 Elsevier Ltd. All rights reserved.