Dryden S, Frankish H M, Wang Q, Williams G
Department of Medicine, University of Liverpool, UK.
Brain Res. 1996 Jun 17;724(2):232-7. doi: 10.1016/0006-8993(96)00329-0.
Neurons containing serotonin (5-HT), a potent anorexic agent, come into contact with neuropeptide Y-ergic neurons, that project from the arcuate nucleus (ARC) to the paraventricular nucleus (PVN). NPY powerfully stimulates feeding and induces obesity when injected repeatedly into PVN. We hypothesize that 5-HT tonically inhibits the ARC-PVN neurons and that balance between the two systems determines feeding and energy homeostasis. This study aimed to determine whether central injection of the 5-HT synthesis inhibitor p-chlorophenylalanine (pCPA), which increases feeding, increased hypothalamic NPY and NPY mRNA levels. pCPA (10 mg/kg in 3 microliters) was administered into the third ventricle either as a single injection (n = 8) or daily for 7 days (n = 8). Control rats received a similar injection of saline. pCPA significantly increased food intake compared with controls after both single and repeated injections (P < 0.05). NPY levels were measured by radioimmunoassay in microdissected hypothalamic extracts. NPY levels in the acutely treated group were significantly increased in the paraventricular nucleus (PVN; by 41%, P = 0.01), anterior hypothalamic area (AHA; by 34%, P < 0.01) and lateral hypothalamic area (LHA; by 41%, P < 0.02). In the 7-day-treated group, NPY levels were also increased in the same areas, i.e. PVN (by 24%, P < 0.01), AHA (by 30%, P < 0.01) and LHA (by 38%, P = 0.01). There were no significant changes in the ARC or any other region or in hypothalamic NPY mRNA levels. pCPA administration increased NPY levels in several regions notably the PVN. This is a major site of NPY release, where NPY injection induces feeding. We suggest that the hyperphagia induced by pCPA is mediated by increased NPY levels and secretion in the PVN. This is further evidence for interactions between NPY and 5-HT in the control of energy homeostasis.
含有血清素（5-羟色胺，一种有效的厌食剂）的神经元与从弓状核（ARC）投射到室旁核（PVN）的神经肽Y能神经元发生接触。当反复注射到室旁核时，神经肽Y会强烈刺激进食并导致肥胖。我们假设血清素持续抑制ARC-PVN神经元，并且这两个系统之间的平衡决定了进食和能量稳态。本研究旨在确定向中枢注射血清素合成抑制剂对氯苯丙氨酸（pCPA）（可增加进食）是否会增加下丘脑神经肽Y和神经肽Y mRNA水平。以单次注射（n = 8）或每日注射7天（n = 8）的方式将pCPA（10毫克/千克，溶于3微升溶液中）注入第三脑室。对照大鼠接受类似的生理盐水注射。单次和重复注射后，与对照组相比，pCPA均显著增加了食物摄入量（P < 0.05）。通过放射免疫分析法在显微解剖的下丘脑提取物中测量神经肽Y水平。急性治疗组的室旁核（PVN；增加41%，P = 0.01）、下丘脑前区（AHA；增加34%，P < 0.01）和下丘脑外侧区（LHA；增加41%，P < 0.02）中的神经肽Y水平显著升高。在7天治疗组中，相同区域（即PVN，增加24%，P < 0.01；AHA，增加30%，P < 0.01；LHA，增加38%，P = 0.01）的神经肽Y水平也升高。弓状核或任何其他区域以及下丘脑神经肽Y mRNA水平均无显著变化。给予pCPA会增加几个区域尤其是室旁核中的神经肽Y水平。这是神经肽Y释放的主要部位，在此处注射神经肽Y会诱导进食。我们认为pCPA诱导的食欲亢进是由室旁核中神经肽Y水平和分泌增加介导的。这是神经肽Y与血清素在能量稳态控制中相互作用的进一步证据。
