Activating mu-opioid receptors in the lateral parabrachial nucleus increases c-Fos expression in forebrain areas associated with caloric regulation, reward and cognition.

Activating mu-opioid receptors in the lateral parabrachial nucleus increases c-Fos expression in forebrain areas associated with caloric regulation, reward and cognition.
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DOI:
10.1016/j.neuroscience.2009.04.071
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发表时间:
2009-08-18
期刊:
影响因子:
3.3
通讯作者:
Simansky, K. J.
Simansky, K. J.
中科院分区:
医学3区
文献类型:
--
作者:
Denbleyker, M.;Nicklous, D. M.;Wagner, P. J.;Ward, H. G.;Simansky, K. J.

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脑桥臂旁核(PBN)参与了摄食的调节,并含有高水平的μ-阿片受体(MOPR)。在以前的工作中,通过将高选择性MOPR激动剂[d-Ala 2,N-Me-Phe 4,Gly 5-ol]脑啡肽(DAMGO)注入外侧臂旁区(LPBN)来刺激MOPR,增加食物摄入。高选择性MOPR拮抗剂d-Phe-Cys-Trp-Arg-Thr-Pen-Thr-NH 2(CTAP)可阻断DAMGO的吞噬作用。本实验旨在分析LPBN中的神经激活模式和与MOPR激活相关的潜在细胞过程。雄性Sprague-Dawley大鼠接受单侧微量输注接近最大高吞噬剂量的DAMGO进入LPBN。然后,我们确定了整个大脑区域的c-Fos免疫反应性水平。激活LPBN的MOPR可增加LPBN以及丘脑腹外侧核、下丘脑弓状核、丘脑室旁核和海马的c-Fos。用CTAP预处理阻止了这些区域中c-Fos翻译的增加。CTAP还阻止了MOPR与其G蛋白的偶联,这通过[35 S]GTPγS放射自显影来测量。总之,这些数据强烈表明,增加MOPR与LPBN中的G蛋白的偶联会抑制臂旁神经元,其随后导致与摄食中的热量调节、摄食奖励和认知过程相关的区域中的神经元的兴奋。
The pontine parabrachial nucleus (PBN) has been implicated in the modulation of ingestion and contains high levels of μ-opioid receptors (MOPRs). In previous work, stimulating MOPRs by infusing the highly selective MOPR agonist [d-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAMGO) into the lateral parabrachial region (LPBN) increased food intake. The highly selective MOPR antagonist d-Phe-Cys-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) prevented the hyperphagic action of DAMGO. The present experiments aimed to analyze both the pattern of neural activation and the underlying cellular processes associated with MOPR activation in the LPBN. Male Sprague-Dawley rats received a unilateral microinfusion of a nearly maximal hyperphagic dose of DAMGO into the LPBN. We then determined the level of c-Fos immunoreactivity in regions throughout the brain. MOPR activation in the LPBN increased c-Fos in the LPBN and in the nucleus accumbens, hypothalamic arcuate nucleus, paraventricular nucleus of the thalamus and hippocampus. Pretreatment with CTAP prevented the increase in c-Fos translation in each of these areas. CTAP also prevented the coupling of MOPRs to their G-proteins which was measured by [35S]GTPγS autoradiography. Together, these data strongly suggest that increasing the coupling of MOPRs to their G-proteins in the LPBN disinhibits parabrachial neurons which subsequently leads to excitation of neurons in regions associated with caloric regulation, ingestive reward and cognitive processes in feeding.
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