Intranasal application of vasopressin fails to elicit changes in brain immediate early gene expression, neural activity and behavioural performance of rats.

Intranasal application of vasopressin fails to elicit changes in brain immediate early gene expression, neural activity and behavioural performance of rats.
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DOI:
10.1111/jne.12046
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发表时间:
2013-07
影响因子:
3.2
通讯作者:
Leng G
Leng G
中科院分区:
医学3区
文献类型:
--
作者:
Ludwig M;Tobin VA;Callahan MF;Papadaki E;Becker A;Engelmann M;Leng G

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鼻内给药已被广泛用于研究神经肽血管加压素和催产素对人类行为和神经系统疾病的影响,但当这些神经肽鼻内给药时究竟会发生什么还远不清楚。特别是,尚不清楚是否有生理上显著量的肽进入大脑以解释所观察到的效应。在这里,我们研究了是否鼻内给药加压素和催产素诱导表达的即刻早期基因产物Fos在大脑区域是敏感的集中管理的肽,它是否改变神经元活动的方式,集中管理的肽,以及它是否影响行为的方式预期从集中管理的肽的研究。我们发现,而脑室内(icv)注射非常低剂量的加压素或催产素增加Fos的表达在几个不同的大脑区域,鼻内给药的大剂量的肽没有显着的效果。与加压素局部应用于主嗅球的效果相反,我们没有看到鼻内加压素给药后嗅球二尖瓣细胞的电活动发生变化。此外,加压素鼻内给药对社会识别或短期识别记忆没有显着影响。最后,鼻内注射加压素对高架十字迷宫(一种啮齿动物焦虑模型)的参数监测没有显著影响。我们在大鼠中的数据表明,鼻内给药后,显著量的加压素和催产素不能以足以改变立即早期基因表达、神经活性或行为的水平到达脑中的区域,所述改变的方式是针对肽的中枢给药所描述的。
Intranasal administration has been widely used to investigate effects of the neuropeptides vasopressin and oxytocin on human behaviors and neurological disorders, but exactly what happens when these neuropeptides are administered intranasally is far from clear. In particular, it is not clear whether a physiological significant amount of peptide enters the brain to account for the observed effects. Here, we investigated whether intranasal administration of vasopressin and oxytocin to rats induces expression of the immediate-early gene product Fos in brain areas that are sensitive to centrally administered peptide, whether it alters neuronal activity in the way that centrally administered peptide does, and whether it affects behavior in ways expected from studies of centrally administered peptide. We found that, whereas intracerebroventricular (icv) injection of very low doses of vasopressin or oxytocin increased Fos expression in several distinct brain regions, intranasal administration of large doses of the peptides had no significant effect. In contrast to the effects of vasopressin applied topically to the main olfactory bulb, we saw no changes in the electrical activity of olfactory bulb mitral cells after intranasal vasopressin administration. In addition, vasopressin given intranasally had no significant effects on social recognition or short-term recognition memory. Finally, intranasal infusions of vasopressin had no significant effects on the parameters monitored on the elevated plus maze, a rodent model of anxiety. Our data in rats suggest that, after intranasal administration, significant amounts of vasopressin and oxytocin do not reach areas in the brain at levels sufficient to change immediate early gene expression, neural activity or behavior in the ways described for central administration of the peptides.
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发表时间: 2012-03
影响因子: 3.5
作者:
Churchland, Patricia S.;Winkielman, Piotr
通讯作者: Winkielman, Piotr
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期刊: NATURE
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