INHIBITION OF OPIOID SYSTEMS IN THE HYPOTHALAMUS AS WELL AS THE MESOLIMBIC AREA SUPPRESSES FEEDING BEHAVIOR OF MICE
INHIBITION OF OPIOID SYSTEMS IN THE HYPOTHALAMUS AS WELL AS THE MESOLIMBIC AREA SUPPRESSES FEEDING BEHAVIOR OF MICE
复制标题
DOI：
10.1016/j.neuroscience.2015.10.002
复制
发表时间：
2015-12-17
期刊：
影响因子：
3.3
通讯作者：
Kamei, J.
中科院分区：
文献类型：
--
作者：
Ikeda, H.;Ardianto, C.;Kamei, J.
据报道，位于腹侧被盖区(VTA)和伏隔核(NAcc)的阿片受体，尤其是Mu-阿片受体，可以调节食物动机。然而，u-阿片受体、β-阿片受体和kappa-阿片受体的作用还不完全清楚。此外，由于Mu阿片受体、德尔塔阿片受体和kappa阿片受体被报道分布在下丘脑，这些受体可能调节摄食行为。因此，本研究调查了VTA、NAcc和下丘脑中的Mu阿片受体、Delta阿片受体和Kappa阿片受体在调节摄食行为中的作用。采用逆转录-聚合酶链式反应(RT-PCR)检测内源性阿片肽前体前阿片黑素皮质素(POMC)、前脑啡肽原(PENK)和前强啡肽原(PDYN)的基因表达水平。全身注射非选择性阿片受体拮抗剂(纳洛酮)和选择性阿片受体拮抗剂MU(β-FNA；β-FNA)、Delta(纳曲多)和kappa(去甲肾上腺素；NorBNI)显著减少摄食量。相比之下，全身注射优先选择的MU(吗啡)、选择性的Delta(KNT-127)和Kappa(U-50,488)阿片受体激动剂并没有改变摄食量。禁食后，下丘脑和中脑的POMC、PENK和PDYN的mRNA水平下降，腹侧纹状体的PENK和PDYN的mRNA水平下降，而POMC的mRNA水平没有下降。向NAcc、VTA和下丘脑外侧核(LH区)注射纳洛酮，但不注射下丘脑腹内侧核，显著减少摄食量。向LH区注射β-FNA和纳曲肽，但不注射VTA或NAcc，则会减少摄食量。向LH区和VTA区注射去甲BNI，但不向NAcc区注射，可减少摄食量。这些结果表明，与VTA和NAcc中的受体相比，LHu-阿片受体、β-阿片受体和kappa-阿片受体在调节摄食行为中起着更重要的作用。(C)2015年IBRO。爱思唯尔有限公司出版。保留所有权利。
Opioid receptors, especially mu-opioid receptors, in the ventral tegmental area (VTA) and nucleus accumbens (NAcc) are reported to regulate food motivation. However, the roles of mu-, delta- and kappa-opioid receptors are not fully understood. Moreover, since mu-, delta- and kappa-opioid receptors are reported to distribute in the hypothalamus, these receptors in the hypothalamus might regulate feeding behavior. Thus, the present study investigated the role of mu-, delta- and kappa-opioid receptors in the VTA, the NAcc and the hypothalamus in the regulation of feeding behavior. Male ICR mice were subjected to a feeding test after food deprivation for 16 h. The mRNA levels of proopiomelanocortin (POMC), preproenkephalin (PENK) and prodynorphin (PDYN), the precursors of endogenous opioid peptides, were measured by reverse transcription-polymerase chain reaction (RT-PCR). The systemic injection of non-selective (naloxone) and selective mu (beta-funaltrexamine; beta-FNA), delta (naltrindole) and kappa (norbinaltorphimine; norBNI) opioid receptor antagonists markedly reduced food intake. In contrast, the systemic injection of preferential mu (morphine), selective delta (KNT-127) and kappa (U-50,488) opioid receptor agonists did not change food intake. The mRNA levels of POMC, PENK and PDYN were decreased in the hypothalamus and the midbrain after food deprivation, whereas the mRNA levels of PENK and PDYN, but not POMC, were decreased in the ventral striatum. The injection of naloxone into the NAcc, VTA and lateral hypothalamus (LH), but not the ventromedial nucleus of the hypothalamus, significantly decreased food intake. The injection of beta-FNA and naltrindole into the LH, but not the VTA or NAcc, decreased food intake. The injection of norBNI into the LH and VTA, but not the NAcc, decreased food intake. These results indicate that mu-, delta- and kappa-opioid receptors in the LH play a more important role in the regulation of feeding behavior than those receptors in the VTA and the NAcc. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.