Inhaled vasopressin increases sociability and reduces body temperature and heart rate in rats
Inhaled vasopressin increases sociability and reduces body temperature and heart rate in rats
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DOI：
10.1016/j.psyneuen.2014.04.013
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发表时间：
2014-08
影响因子：
3.7
通讯作者：
Linnet Ramos;Callum Hicks;Alex Caminer;I. McGregor
中科院分区：
文献类型：
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作者：
Linnet Ramos;Callum Hicks;Alex Caminer;I. McGregor
神经肽加压素 (AVP) 和催产素 (OT) 对一系列精神疾病具有治疗潜力。然而，通常用于递送这些神经肽的鼻内给药途径的有效性存在不确定性。最近的临床前研究（通常涉及麻醉或束缚动物）评估了鼻内 AVP 或 OT 效应，并获得了有些不一致的结果。在此，我们通过将肽（1 ml 5 或 10 mg/ml 溶液）雾化到一个封闭的小室中，历时 2 分钟，对大鼠进行 AVP 鼻内给药，其中放置了习惯良好、未麻醉、不受约束的大鼠。立即将大鼠从室中移出并进行社交互动测试，或使用生物遥测技术评估心率和体温的变化。结果表明，暴露于雾化 AVP（5 或 10 mg/ml）的大鼠在社交互动测试中表现出社交接近度增加（邻卧）和肛门生殖器嗅探减少。生物遥测显示雾化 AVP 具有显着且持久（>1 小时）的体温过低和心动过缓效应。雾化 AVP 的这些行为和生理效应类似于最近外周注射 AVP 研究中观察到的结果。雾化 AVP 后 10 分钟，血浆 AVP 浓度大幅增加，产生的水平高于行为有效的 AVP 注射剂量（0.005 mg/kg 腹膜内注射）所见的水平。因此，本研究为啮齿类动物施用神经肽提供了一种新颖且有效的方法。
The neuropeptides vasopressin (AVP) and oxytocin (OT) have therapeutic potential across a range of psychiatric disorders. However, there is uncertainty about the effectiveness of the intranasal route of administration that is often used to deliver these neuropeptides. Recent preclinical studies, typically involving anesthetized or restrained animals, have assessed intranasal AVP or OT effects, and have obtained somewhat inconsistent results. Here we obtained intranasal administration of AVP in rats by nebulizing the peptide (1 ml of 5 or 10 mg/ml solution) into a small enclosed chamber over a 2 min period in which well-habituated, unanesthetized, unrestrained, rats were placed. Rats were immediately removed from the chamber and tested in the social interaction test, or assessed for changes in heart rate and body temperature using biotelemetry. Results showed that rats exposed to nebulized AVP (5 or 10 mg/ml) showed increased social proximity (adjacent lying) and decreased anogenital sniffing in the social interaction test. Biotelemetry showed substantial and long lasting (>1 h) hypothermic and bradycardic effects of nebulized AVP. These behavioral and physiological effects of nebulized AVP mimic those observed in recent studies with peripherally injected AVP. Plasma AVP concentrations were substantially increased 10 min after nebulized AVP, producing levels above those seen with a behaviorally effective injected dose of AVP (0.005 mg/kg intraperitoneal). This study thus provides a novel and effective method for neuropeptide administration to rodents.