Ramos Linnet, Hicks Callum, Caminer Alex, McGregor Iain S
School of Psychology, Brennan MacCallum Building, University of Sydney, NSW 2006, Australia.
School of Psychology, Brennan MacCallum Building, University of Sydney, NSW 2006, Australia.
Psychoneuroendocrinology. 2014 Aug;46:46-51. doi: 10.1016/j.psyneuen.2014.04.013. Epub 2014 Apr 24.
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 (1ml of 5 or 10mg/ml solution) into a small enclosed chamber over a 2min 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 10mg/ml) showed increased social proximity (adjacent lying) and decreased anogenital sniffing in the social interaction test. Biotelemetry showed substantial and long lasting (>1h) 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 10min after nebulized AVP, producing levels above those seen with a behaviorally effective injected dose of AVP (0.005mg/kg intraperitoneal). This study thus provides a novel and effective method for neuropeptide administration to rodents.
神经肽血管加压素（AVP）和催产素（OT）在一系列精神疾病中具有治疗潜力。然而，常用于递送这些神经肽的鼻内给药途径的有效性尚不确定。最近的临床前研究，通常涉及麻醉或受限动物，评估了鼻内AVP或OT的作用，并获得了有些不一致的结果。在这里，我们通过在2分钟内将肽（1ml 5或10mg/ml溶液）雾化到一个小的封闭腔室中，在其中放置适应良好、未麻醉、不受限的大鼠，从而实现对大鼠进行鼻内给予AVP。大鼠立即从腔室中移出，并在社交互动测试中进行测试，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10mg/ml）的大鼠在社交互动测试中表现出增加的社交亲近度（相邻躺卧）和减少的肛门生殖器嗅探。生物遥测显示雾化AVP具有显著且持久（>1小时）的降温及心动过缓作用。雾化AVP的这些行为和生理效应与近期外周注射AVP的研究中观察到的效应相似。雾化AVP后10分钟，血浆AVP浓度大幅升高，产生的水平高于行为有效注射剂量的AVP（0.005mg/kg腹腔注射）所观察到的水平。因此，本研究为向啮齿动物给药神经肽提供了一种新颖且有效的方法。
