From the stomach to locus coeruleus: new neural substrate for ghrelin's effects on ingestive, motivated and anxiety-like behaviors.
From the stomach to locus coeruleus: new neural substrate for ghrelin's effects on ingestive, motivated and anxiety-like behaviors.
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DOI：
10.3389/fphar.2023.1286805
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发表时间：
2023
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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胃饥饿素是一种胃源性的食欲激素，在能量稳态、食物奖励和情绪方面具有公认的作用。蓝斑的去甲肾上腺素能神经元在唤醒、情绪、认知等方面发挥重要作用，近年来也被认为参与摄食行为的控制。生长激素促分泌素受体（生长激素促分泌素受体，GHSR）可能存在于LC中，但生长激素促分泌素信号传导在该区域中的行为效应仍然未被探索。在这里，我们首先确定是否GHSR存在于大鼠LC，并证明GHSR表达的去甲肾上腺素能神经元在两种性别。接下来，我们研究了ghrelin是否通过在LC中起作用来控制摄食和动机行为以及焦虑样行为。为了追求这个想法，我们研究了LC GHSR刺激和阻断对食物摄入的影响，对美味食物奖励的操作性反应，以及在开放领域（OF）和声学惊吓反应（ASR）测试中的焦虑样行为。我们的研究结果表明，内LC生长激素释放肽管理增加食物的摄入量和动机行为的蔗糖在两种性别。此外，雌性动物（而非雄性动物）在ASR中表现出强效抗焦虑反应。为了确定LC中GHSR的激活是否是进食和焦虑行为控制所必需的，我们利用肝脏表达的抗菌肽2（LEAP 2），一种新鉴定的内源性GHSR拮抗剂。LEAP 2专门交付到LC是足以减少禁食诱导的食物暴食症在两种性别，但食物奖励只在女性。此外，在两种性别中，在ASR测试中测量的LC中GHSR的阻断增加了焦虑样行为。两者合计，这些结果表明，生长激素释放肽的行为在LC改变摄食，动机和焦虑样行为，与一定程度的性别差异。
Ghrelin, a stomach-derived orexigenic hormone, has a well-established role in energy homeostasis, food reward, and emotionality. Noradrenergic neurons of the locus coeruleus (LC) are known to play an important role in arousal, emotion, cognition, but recently have also been implicated in control of feeding behavior. Ghrelin receptors (the growth hormone secretagogue receptor, GHSR) may be found in the LC, but the behavioral effects of ghrelin signaling in this area are still unexplored. Here, we first determined whether GHSR are present in the rat LC, and demonstrate that GHSR are expressed on noradrenergic neurons in both sexes. We next investigated whether ghrelin controls ingestive and motivated behaviors as well as anxiety-like behavior by acting in the LC. To pursue this idea, we examined the effects of LC GHSR stimulation and blockade on food intake, operant responding for a palatable food reward and, anxiety-like behavior in the open field (OF) and acoustic startle response (ASR) tests in male and female rats. Our results demonstrate that intra-LC ghrelin administration increases chow intake and motivated behavior for sucrose in both sexes. Additionally, females, but not males, exhibited a potent anxiolytic response in the ASR. In order to determine whether activation of GHSR in the LC was necessary for feeding and anxiety behavior control, we utilized liver-expressed antimicrobial peptide 2 (LEAP2), a newly identified endogenous GHSR antagonist. LEAP2 delivered specifically into the LC was sufficient to reduce fasting-induced chow hyperphagia in both sexes, but food reward only in females. Moreover, blockade of GHSR in the LC increased anxiety-like behavior measured in the ASR test in both sexes. Taken together, these results indicate that ghrelin acts in the LC to alter ingestive, motivated and anxiety-like behaviors, with a degree of sex divergence.
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影响因子：
15.9
作者：
Chuang, Jen-Chieh;Perello, Mario;Zigman, Jeffrey M.
通讯作者：
Zigman, Jeffrey M.
影响因子：
15.9
作者：
Abizaid, Alfonso;Liu, Zhong-Wu;Horvath, Tamas L.
通讯作者：
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DOI：
10.1016/s0006-291x(02)02740-7
发表时间：
2002-12-20
影响因子：
3.1
作者：
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通讯作者：
de Barioglio, SR
影响因子：
3.4
作者：
Jerlhag, Elisabet;Egecioglu, Emil;Engel, Jorgen A.
通讯作者：
Engel, Jorgen A.
影响因子：
5.2
作者：
通讯作者：
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