Dryden S, Wang Q, Frankish H M, Pickavance L, Williams G
Department of Medicine, University of Liverpool, UK.
Brain Res. 1995 Nov 13;699(1):12-8. doi: 10.1016/0006-8993(95)00841-d.
NPY is synthesized in neurons of the hypothalamic arcuate nucleus (ARC) which project to the paraventricular nucleus (PVN), an important site of NPY release. Serotonin (5-HT) has been suggested to induce satiety and 5-HT fibers contact NPY neurons in the ARC and PVN, suggesting that 5-HT could inhibit the ARC-PVN projection. Methysergide is a 5-HT antagonist which stimulates feeding in rats and increases NPY levels in the hypothalamus. To clarify the effects of methysergide on NPY, we examined its effects on NPY synthesis and on NPY secretion in the PVN using push-pull sampling. Hypothalamic NPY mRNA levels were measured in rats (n = 8/group) given either saline or methysergide (10 mg/kg) and killed after 4 h or after 7 days. Food intake was increased by 33% in the acute study and by 9% in the 7-day study (both P < 0.01). NPY mRNA levels were 80% higher in the 7-day study (P < 0.05) and unchanged in the acute study. NPY secretion was measured over a 3-h period after an i.p. injection of methysergide or saline (10 mg/kg, n = 12) with a flow rate of 15 microliters/min. Mean NPY secretion in the methysergide-injected rats was increased by 34% (P < 0.01). We conclude that methysergide induced feeding is associated with increased activity of the NPY neurons in the ARC-PVN projection. This is consistent with our previous findings suggesting that the NPYergic ARC-PVN projection may mediate, at least in part the effects of 5-HT on feeding and energy balance.
神经肽Y（NPY）在下丘脑弓状核（ARC）的神经元中合成，这些神经元投射到室旁核（PVN），而PVN是NPY释放的重要部位。血清素（5-HT）被认为可诱导饱腹感，且5-HT纤维与ARC和PVN中的NPY神经元接触，这表明5-HT可能抑制ARC-PVN投射。麦角新碱是一种5-HT拮抗剂，可刺激大鼠进食并增加下丘脑中NPY的水平。为了阐明麦角新碱对NPY的影响，我们使用推挽式采样法研究了其对PVN中NPY合成和NPY分泌的作用。给大鼠（每组n = 8）注射生理盐水或麦角新碱（10 mg/kg），4小时或7天后处死，测量下丘脑NPY mRNA水平。急性研究中食物摄入量增加了33%，7天研究中增加了9%（均P < 0.01）。7天研究中NPY mRNA水平升高了80%（P < 0.05），急性研究中则无变化。腹腔注射麦角新碱或生理盐水（10 mg/kg，n = 12）后，以15微升/分钟的流速在3小时内测量NPY分泌。注射麦角新碱的大鼠中NPY平均分泌增加了34%（P < 0.01）。我们得出结论，麦角新碱诱导的进食与ARC-PVN投射中NPY神经元的活性增加有关。这与我们之前的研究结果一致，即含NPY的ARC-PVN投射可能至少部分介导了5-HT对进食和能量平衡的影响。
