Dryden S, Frankish H M, Wang Q, Pickavance L, Williams G
Department of Medicine, University of Liverpool, U.K.
Neuroscience. 1996 May;72(2):557-66. doi: 10.1016/0306-4522(95)00566-8.
Evidence suggests that serotonin and neuropeptide Y neurons in the hypothalamus, which respectively inhibit and stimulate food intake, may interact to control energy homoeostasis. We therefore investigated the effects of fluoxetine, which inhibits serotonin reuptake, on food intake and the activity of the neuropeptide Yergic arcuato-paraventricular projection in lean Wistar and Zucker rats. We also studied its effects in obese Zucker rats, in which obesity is postulated to be due to overactivity of the arcuato-paraventricular projection. Fluoxetine significantly reduced food intake in lean and obese rats, both during continuous subcutaneous infusion and (10 mg/kg/day for seven days) and acutely after a single injection (10 mg/kg). Fluoxetine also significantly reduced neuropeptide Y levels in the paraventricular nucleus, a major site of neuropeptide Y release which is highly sensitive to the appetite-stimulating actions of neuropeptide Y. Push-pull sampling in lean and fatty Zucker rats showed that neuropeptide Y secretion in the paraventricular nucleus was significantly reduced after acute fluoxetine treatment. Furthermore, seven days fluoxetine treatment prevented the significant increases in hypothalamic neuropeptide Y messenger RNA which were induced in lean rats by food restriction which precisely matched the hypophagia induced by the drug. We conclude that fluoxetine inhibits various aspects of the activity of the neuropeptide Yergic arcuato-paraventricular neurons, and suggest that reduced neuropeptide Y release in the paraventricular nucleus may mediate, at least in part, the drug's hypophagic action. We further suggest that serotonin may influence food intake and energy balance by inhibiting the arcuato-paraventricular projection, and that the two neurotransmitters may act together to regulate feeding and energy homoeostasis.
有证据表明，下丘脑的5-羟色胺能神经元和神经肽Y能神经元分别抑制和刺激食物摄取，它们可能相互作用以控制能量稳态。因此，我们研究了抑制5-羟色胺再摄取的氟西汀对瘦的Wistar大鼠和Zucker大鼠食物摄取及神经肽Y能的弓状核-室旁核投射活性的影响。我们还研究了其在肥胖Zucker大鼠中的作用，据推测肥胖Zucker大鼠的肥胖是由于弓状核-室旁核投射过度活跃所致。在连续皮下输注期间（10mg/kg/天，共7天）以及单次注射（10mg/kg）后急性给药时，氟西汀均能显著减少瘦大鼠和肥胖大鼠的食物摄取。氟西汀还能显著降低室旁核中的神经肽Y水平，室旁核是神经肽Y释放的主要部位，对神经肽Y的促食欲作用高度敏感。对瘦的和肥胖的Zucker大鼠进行推挽式采样显示，急性氟西汀治疗后室旁核中的神经肽Y分泌显著减少。此外，氟西汀治疗7天可防止食物限制诱导的瘦大鼠下丘脑神经肽Y信使核糖核酸的显著增加，食物限制诱导的下丘脑神经肽Y信使核糖核酸增加与该药物诱导的摄食减少精确匹配。我们得出结论，氟西汀抑制神经肽Y能的弓状核-室旁核神经元活性的各个方面，并提示室旁核中神经肽Y释放减少可能至少部分介导了该药物的摄食减少作用。我们进一步提示，5-羟色胺可能通过抑制弓状核-室旁核投射来影响食物摄取和能量平衡，并且这两种神经递质可能共同作用来调节进食和能量稳态。
