Differential Changes in Expression of Stress- and Metabolic-Related Neuropeptides in the Rat Hypothalamus during Morphine Dependence and Withdrawal.
Differential Changes in Expression of Stress- and Metabolic-Related Neuropeptides in the Rat Hypothalamus during Morphine Dependence and Withdrawal.
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吗啡依赖性和戒断期间，大鼠下丘脑中应激和代谢相关的神经肽表达的差异变化。
DOI：
10.1371/journal.pone.0067027
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Kovács KJ
中科院分区：
文献类型：
--
作者：
Pintér-Kübler B;Ferenczi S;Núnez C;Zelei E;Polyák A;Milanés MV;Kovács KJ
慢性吗啡治疗和纳洛酮催促的吗啡戒断激活了应激相关的脑回路，并导致摄食量、体重增加和能量代谢的显著变化。本研究旨在揭示这些作用的下丘脑机制。通过皮下植入持续释放的药物微丸使成年雄性大鼠产生吗啡依赖。配对喂养显示吗啡治疗大鼠的体重减轻显着较小的安慰剂植入动物相比，其食物消耗量仅限于吗啡植入对吃。这些结果表明吗啡处理的动物的能量消耗减少。与植入安慰剂和配对喂养的动物相比，慢性吗啡暴露或配对喂养并不显著影响下丘脑中所选应激和代谢相关神经肽-促肾上腺皮质激素释放激素（CRH）、尿皮质素2（UCN 2）和阿黑皮素原（POMC）的表达。吗啡依赖大鼠注射纳洛酮后15-30 min体重显著下降，血浆促肾上腺皮质激素、催乳素和皮质酮水平升高。采用实时定量PCR监测下丘脑神经肽mRNA相对表达的时间过程，我们发现CRH和UCN 2 mRNA升高，POMC表达显着降低。神经肽Y（NPY）和精氨酸加压素（AVP）的mRNA水平在阿片戒断过程中短暂增加。这些数据突出表明，吗啡戒断差异影响应激和代谢相关的神经肽在大鼠下丘脑的表达，而这些神经肽的相对mRNA水平保持不变，无论是在大鼠长期治疗吗啡或在其配对喂养的控制。
Chronic morphine treatment and naloxone precipitated morphine withdrawal activates stress-related brain circuit and results in significant changes in food intake, body weight gain and energy metabolism. The present study aimed to reveal hypothalamic mechanisms underlying these effects. Adult male rats were made dependent on morphine by subcutaneous implantation of constant release drug pellets. Pair feeding revealed significantly smaller weight loss of morphine treated rats compared to placebo implanted animals whose food consumption was limited to that eaten by morphine implanted pairs. These results suggest reduced energy expenditure of morphine-treated animals. Chronic morphine exposure or pair feeding did not significantly affect hypothalamic expression of selected stress- and metabolic related neuropeptides - corticotropin-releasing hormone (CRH), urocortin 2 (UCN2) and proopiomelanocortin (POMC) compared to placebo implanted and pair fed animals. Naloxone precipitated morphine withdrawal resulted in a dramatic weight loss starting as early as 15–30 min after naloxone injection and increased adrenocorticotrophic hormone, prolactin and corticosterone plasma levels in morphine dependent rats. Using real-time quantitative PCR to monitor the time course of relative expression of neuropeptide mRNAs in the hypothalamus we found elevated CRH and UCN2 mRNA and dramatically reduced POMC expression. Neuropeptide Y (NPY) and arginine vasopressin (AVP) mRNA levels were transiently increased during opiate withdrawal. These data highlight that morphine withdrawal differentially affects expression of stress- and metabolic-related neuropeptides in the rat hypothalamus, while relative mRNA levels of these neuropeptides remain unchanged either in rats chronically treated with morphine or in their pair-fed controls.
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DOI：
10.1073/pnas.0707585104
发表时间：
2007-10-23
影响因子：
11.1
作者：
George, Olivier;Ghozland, Sandy;Koob, George F.
通讯作者：
Koob, George F.
影响因子：
3.5
作者：
Kas, MJH;Bruijnzeel, AW;Adan, RAH
通讯作者：
Adan, RAH
DOI：
10.1196/annals.1417.028
发表时间：
2008-01-01
期刊：
MOLECULAR AND BIOPHYSICAL MECHANISMS OF AROUSAL, ALERTNESS, AND ATTENTION
影响因子：
--
作者：
Befort, K.;Filliol, D.;Kieffer, B. L.
通讯作者：
Kieffer, B. L.
影响因子：
2.9
作者：
De Fanti, BA;Martínez, JA
通讯作者：
Martínez, JA
DOI：
10.1111/j.1600-0773.1992.tb00540.x
发表时间：
1992-09-01
期刊：
PHARMACOLOGY & TOXICOLOGY
影响因子：
--
作者：
KAUPPILA, T;MECKE, E;PERTOVAARA, A
通讯作者：
PERTOVAARA, A