Laboratory of Molecular Neuroendocrinology, Institute of Experimental Medicine, P.O. Box 67, H-1450 Budapest, Hungary.
Neurochem Int. 2010 Oct;57(3):323-30. doi: 10.1016/j.neuint.2010.06.011. Epub 2010 Jun 26.
To reveal neuroendocrine/neurochemical changes that are responsible for the robust metabolic alterations seen during chronic morphine treatment we followed hormonal-, transcriptional- and behavioral changes during chronic morphine administration in adult male Wistar rats. Animals were implanted with increasing amount of slow release morphine tablets for 8 days. Morphine treated animals gain significantly less weight than placebo implanted controls. This weight loss is due to the dramatic decrease in the food intake and caloric efficiency in the first days of drug administration and to the lasting disregulated feeding pattern. Changes in feeding behavior included increase of diurnal and decrease of nocturnal feeding frequency in morphine treated rats. Significantly less leptin and insulin plasma levels were detected in morphine implanted animals than in placebo implanted controls, while adiponectin and ACTH concentration remain unchanged. Morphine treated rats display an increase of FosB/Delta FosB immunoreactivity at brain sites that have been implicated regulation of food intake and energy expenditure, including hypothalamic arcuate, paraventricular and ventromedial nuclei and in the lateral hypothalamic area as well as in the caudal brainstem. However, morphine-induced long-term metabolic alterations were not accompanied with any significant changes in the expression of anorexigenic neuropeptides POMC and CART in the hypothalamus and in the brainstem. The disregulated feeding pattern was not reflected in changes of orexin transcription, however, a compensatory upregulation was revealed in hypothalamic NPY expression.
为了揭示慢性吗啡治疗期间发生的强大代谢改变的神经内分泌/神经化学变化，我们在成年雄性 Wistar 大鼠中观察了慢性吗啡给药期间的激素、转录和行为变化。动物被植入逐渐增加剂量的缓释吗啡片 8 天。与接受安慰剂植入的对照组相比，吗啡处理的动物体重明显减轻。这种体重减轻是由于药物治疗的前几天食物摄入量和热量效率的急剧下降，以及持续失调的喂养模式。喂养行为的变化包括吗啡处理大鼠的日间进食频率增加和夜间进食频率减少。与接受安慰剂植入的对照组相比，吗啡植入动物的瘦素和胰岛素血浆水平显著降低，而脂联素和 ACTH 浓度保持不变。吗啡处理的大鼠在大脑中与调节食物摄入和能量消耗有关的部位，包括下丘脑弓状核、室旁核和腹内侧核以及外侧下丘脑区域以及尾状脑干，显示出 FosB/Delta FosB 免疫反应性增加。然而，吗啡诱导的长期代谢改变并没有伴随着下丘脑和脑干中厌食神经肽 POMC 和 CART 的表达发生任何显著变化。失调的喂养模式没有反映在食欲素转录的变化中，然而，下丘脑 NPY 表达显示出代偿性上调。
