Department of Physiology/Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Medicinaregatan 11, SE-40530 Gothenburg, Sweden.
Neuroscience. 2011 Apr 28;180:201-11. doi: 10.1016/j.neuroscience.2011.02.002. Epub 2011 Feb 15.
The orexigenic and pro-obesity hormone ghrelin targets key hypothalamic and mesolimbic circuits involved in energy balance, appetite and reward. Given that such circuits are closely integrated with those regulating mood and cognition, we sought to determine whether chronic (>2 weeks) CNS exposure to ghrelin alters anxiety- and depression-like behaviour in rats as well as some physiological correlates. Rats bearing chronically implanted i.c.v. catheters were treated with ghrelin (10 μg/d) or vehicle for 4 weeks. Tests used to assess anxiety- and depression-like behaviour were undertaken during weeks 3-4 of the infusion. These revealed an increase in anxiety- and depression-like behaviour in the ghrelin-treated rats relative to controls. At the end of the 4-week infusion, brains were removed and the amygdala dissected for subsequent qPCR analysis that revealed changes in expression of a number of genes representing key systems implicated in these behavioural changes. Finally, given the key role of the dorsal raphe serotonin system in emotional reactivity, we examined the electrophysiological response of dorsal raphe neurons after a ghrelin challenge, and found mainly inhibitory responses in this region. We demonstrate that the central ghrelin signalling system is involved in emotional reactivity in rats, eliciting pro-anxiety and pro-depression effects and have begun to explore novel target systems for ghrelin that may be of importance for these effects.
食欲刺激和致肥胖激素 ghrelin 作用于参与能量平衡、食欲和奖赏的关键下丘脑和中脑边缘回路。鉴于这些回路与调节情绪和认知的回路密切整合，我们试图确定慢性（>2 周）中枢神经系统暴露于 ghrelin 是否会改变大鼠的焦虑和抑郁样行为以及一些生理相关性。具有慢性植入的 icv 导管的大鼠接受 ghrelin（10 μg/d）或载体治疗 4 周。在输注的第 3-4 周进行用于评估焦虑和抑郁样行为的测试。这些测试表明，ghrelin 处理的大鼠相对于对照大鼠表现出焦虑和抑郁样行为增加。在 4 周输注结束时，取出大脑并解剖杏仁核进行随后的 qPCR 分析，该分析揭示了代表涉及这些行为变化的关键系统的许多基因表达的变化。最后，鉴于背侧中缝核 5-羟色胺系统在情绪反应中的关键作用，我们检查了 ghrelin 挑战后背侧中缝核神经元的电生理反应，发现该区域主要存在抑制反应。我们证明，中枢 ghrelin 信号系统参与大鼠的情绪反应，引起促焦虑和促抑郁作用，并已开始探索 ghrelin 的新靶系统，这些系统可能对这些作用很重要。
