Abstract：
Ghrelin, a hormone secreted by the stomach, binds to the growth hormone secretagogue receptor (GHSR) in various brain regions to produce a number of behavioral effects that include increased feeding motivation. During social defeat stress, ghrelin levels rise in correlation with increased feeding and potentially play a role in attenuating the anxiogenic effects of social defeat. One region implicated in the feeding effects of ghrelin is the ventral tegmental area (VTA), a region implicated in reward seeking behaviors, and linked to social defeat in mice. Here we examined the role of GHSR signaling in the VTA in feeding behavior in mice exposed to social defeat stress. Male C57BL/J6 mice that were socially defeated once daily for 3 weeks ate more, had higher plasma ghrelin level and increased GHSR expression in the VTA compared to non-stressed mice. Socially defeated GHSR KO mice failed to increase their caloric intake in response to this stressor but rescue of GHSR expression in the VTA restored feeding responses. Finally, we pharmacologically blocked VTA GHSR signalling with JMV2959 infused via an indwelling VTA cannula connected to a minipump. Vehicle-treated mice increased their caloric intake during social defeat, but JMV2959-infusions attenuated feeding responses and increased anxiety-like behaviors. The data suggest that GHSR signalling in the VTA is critical for the increases in appetite observed during chronic social defeat stress. Furthermore, these data support the idea that GHSR signaling in the VTA may also have anxiolytic effects, and blocking GHSR in this region may result in an anxiety-like phenotype.
摘要：
Ghrelin,胃分泌的激素,与不同大脑区域的生长激素促分泌素受体（GHSR）结合，产生许多行为效应，包括增加进食动机。在社会失败压力下，ghrelin水平升高与进食增加相关，并可能在减轻社会失败的焦虑作用中发挥作用。与生长素释放肽的摄食作用有关的一个区域是腹侧被盖区（VTA），与寻求奖励行为有关的地区，与老鼠的社会失败有关。在这里，我们研究了GHSR信号在VTA中在暴露于社交失败压力的小鼠的摄食行为中的作用。C57BL/J6雄性小鼠每天被社会打败一次，持续3周，吃得更多，与非应激小鼠相比,在VTA中具有更高的血浆生长素释放肽水平和增加的GHSR表达。社交失败的GHSRKO小鼠未能增加对这种应激源的热量摄入，但在VTA中挽救GHSR表达恢复了进食反应。最后,我们通过与微型泵连接的留置VTA插管输注JMV2959,在药理学上阻断了VTAGHSR信号传导.在社交失败期间，车辆处理的小鼠增加了热量摄入，但是JMV2959输注减弱了进食反应并增加了焦虑样行为。数据表明，VTA中的GHSR信号传导对于在慢性社会失败压力期间观察到的食欲增加至关重要。此外，这些数据支持这样的观点，即VTA中的GHSR信号也可能具有抗焦虑作用，在该区域阻断GHSR可能导致焦虑样表型。
