Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy.
CNS Neurosci Ther. 2012 Jun;18(6):487-92. doi: 10.1111/j.1755-5949.2012.00314.x.
Several studies have documented an involvement of Neuropeptide Y (NPY) in stress-related disorders. Stress-related disorders are also characterized by changes in brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), neurotrophins implicated in the survival and function of neurons. Thus the aim of this study was to investigate whether an NPY intraperitoneal treatment has antidepressant-like effects in rats subjected to a classical stress paradigm, the Forced Swim Test (FST), in association with changes in local brain neurotrophin production.
Rats were intraperitoneally injected with either NPY (60 μg/kg) or a vehicle for three consecutive days between two FST sessions and then tested for time spent (or delay onset) in immobile posture. Moreover, we measured by enzyme-linked immunosorbent assay (ELISA) neurotrophin levels in the hypothalamus and corticosterone levels in plasma.
The data showed that NPY induced a significant delay in the onset and a significant reduction in the duration of the immobility posture in FST. We also found that NPY decreased BDNF levels in the hypothalamus and corticosterone levels in plasma.
Immobility posture in FST can be reduced by antidepressant drugs. Thus, our data show an antidepressant-like effect of NPY associated with changes in BDNF levels in the hypothalamus and reduced activity of hypothalamic-pituitary-adrenal (HPA) axis.
These findings, while confirming the involvement of the NPY system in stress-related disorders, suggest that a less invasive route of administration, such as an intraperitoneal injection, may be instrumental in coping with stressful events in animal models and perhaps in humans.
几项研究记录了神经肽 Y（NPY）在与应激相关的疾病中的作用。与应激相关的疾病的特征还在于脑源性神经营养因子（BDNF）和神经生长因子（NGF）的变化，这些神经营养因子参与神经元的存活和功能。因此，本研究的目的是研究 NPY 腹腔内治疗是否对经历经典应激范式（强迫游泳试验（FST））的大鼠具有抗抑郁样作用，以及与局部脑神经营养因子产生的变化相关。
在两次 FST 之间，连续三天每天给大鼠腹腔注射 NPY（60μg/kg）或载体，然后测试其在不动姿势中的时间（或延迟开始）。此外，我们通过酶联免疫吸附测定（ELISA）测量下丘脑的神经营养因子水平和血浆中的皮质酮水平。
数据显示，NPY 诱导了 FST 中不动姿势开始的明显延迟和持续时间的明显减少。我们还发现 NPY 降低了下丘脑的 BDNF 水平和血浆中的皮质酮水平。
FST 中的不动姿势可以被抗抑郁药减少。因此，我们的数据显示 NPY 具有抗抑郁样作用，与下丘脑的 BDNF 水平变化和下丘脑-垂体-肾上腺（HPA）轴活性降低有关。
这些发现虽然证实了 NPY 系统在与应激相关的疾病中的作用，但表明一种侵入性较小的给药途径，如腹腔内注射，可能有助于动物模型和人类应对应激事件。
