神经肽S及其受体对抑制药物成瘾探究进展.docVIP

神经肽S及其受体对抑制药物成瘾探究进展 　　　 [摘要]神经肽S(NPS)与其受体是一个最近定义的、具有生物活性的多肽物质,有调节压力与兴奋的作用。NPS在脑干中许多不同的部位表达,如在LC区域和臂旁核神经肽S与其同源G蛋白偶联低纳摩尔浓度受体激动剂,诱导细胞内Ca2t水平和cAMP水平。以此作为兴奋传递介质,神经肽S受体在脑中广泛表达,包括调节压力反映的区域,如夏下丘脑、丘脑、扁桃体和边缘皮层。我们知道神经肽S系统具有影响压力、觉醒、恐惧、焦虑、抑郁、学习与记忆、摄食与能量代谢、神经内分泌、免疫和抗氧化等生理病理过程。随着对神经肽S的进一步研究,发现它对于药物成瘾有一定的作用。通过条件大鼠地点喜好、酒精偏好和非酒精偏好高架十字迷宫、自我给药试验等测试,寻找神经肽S与成瘾抑制间的联系。 　　[关键词]神经肽S 神经肽S受体 成瘾 　　 　　【Abstract】Neuropeptide S (NPS) is a recently identified bioactive peptide that modulates stress and arousal. NPS is expressed in a few discrete nuclei in the brainstem, such as the pericoerulear (locus coeruleus (LC)) area and the parabrachial nucleus.NPS activates its cognate G protein-coupled receptor at low nanomolar agonist concentrations and induces elevation of intracellular Ca2t and cAMP, therefore acting as an excitatory transmitter. The NPS receptor is widely expressed in the brain, including regions known to regulate stress responses such as hypothalamus, thalamus, amygdala and limbic cortex. We have recently reported that the NPS system can modulate stress responses and induce wakefulness and appetite control and thus might be a valuable target for development of a new class of drugs to treat anxiety disorders, Fear, anxiety, depression, learning and memory, feeding and energy metabolism, neuroendocrine, immune and anti-oxidation and many other important physiological and pathological processes. Following the research of NPS, The researchers found that have effects to addiction. In the Conditioned place preference, alcohol-preferring and non-preferring rats elevated plus maze, self-adminstration experiments. Finding the relationship between the NPS and addiction. 　　【Key words】Neuropeptide S Neuropeptide S receptor addiction 　　 　　一、引言 　　一个新的肽系统神经肽S已经被分离出来。神经肽S与Gs/Gq蛋白偶联受体结合以前被定义为GPR154,现被称为神经肽S受体。原位杂交脑切片显示神经肽S,主要表达一个先前未知的脑桥色素核,巴林顿核和臂旁核间的神经元群。在脑桥色素核和巴林顿核间的区域,神经肽S mRNA主要表达臂旁核区中的谷氨酸细胞,其表现是重叠的促肾上腺皮质激素释放因子阳性神经元。神经肽S受体mRNA通过中枢神经系统表达,在嗅觉结、杏仁复合体、下脚、外侧、内侧、下丘脑、腹内侧和丘脑室旁核发现很高含量。脑室内注射神经肽S引起神经肽S