Neuroscience Group, Division of Basic Biomedical Sciences, Sanford School of Medicine, The University of South Dakota, 414 E Clark St, Vermillion, SD 57069, USA.
Brain Res Bull. 2011 May 30;85(3-4):117-22. doi: 10.1016/j.brainresbull.2011.03.003. Epub 2011 Mar 9.
Post-weaning social isolation of rats is utilized as a model of early life stress. We have previously demonstrated that rats exposed to post-weaning social isolation exhibit greater anxiety-like behaviors as adults. Furthermore, these rats exhibit greater density of corticotropin-releasing factor (CRF) type 2 receptors in the dorsal raphe nucleus. Therefore, we examined whether antagonism of CRF(2) receptors in the dorsal raphe nucleus reverses the effects of post-weaning social isolation on anxiety states. Male rats were reared in isolation or in groups from day of weaning (postnatal day [PND] 21) to mid-adolescence (PND42) and then allowed to develop to early adulthood housed in groups. At PND62, rats were either infused with vehicle, the CRF(1) receptor antagonist antalarmin (0.25-0.5 μg) or the CRF(2) receptor antagonist antisauvagine-30 (2 μg) into the dorsal raphe nucleus, 20 min prior to being introduced to the elevated plus maze. Isolation-reared rats showed reduced open arm behavior compared to group-reared rats, confirming the anxiogenic effects of post-weaning social isolation. Infusion of the CRF(2) receptor antagonist, but not the CRF(1) receptor antagonist, into the dorsal raphe nucleus of isolation-reared rats increased open arm behavior when compared to that of group-reared rats. Overall, the findings suggest that CRF(2) receptors within the dorsal raphe nucleus mediate anxiety-like states following post-weaning social isolation, and CRF(2) receptors may represent an important target for the treatment of anxiety disorders following early life stressors.
大鼠断奶后社交隔离被用作早期生活应激的模型。我们之前已经证明，经历断奶后社交隔离的大鼠在成年后表现出更严重的焦虑样行为。此外，这些大鼠在背侧中缝核中表现出更高密度的促肾上腺皮质素释放因子（CRF）2 型受体。因此，我们研究了背侧中缝核中 CRF（2）受体的拮抗作用是否可以逆转断奶后社交隔离对焦虑状态的影响。雄性大鼠从断奶日（出生后第 21 天）到青春期中期（第 42 天）被隔离或分组饲养，然后在分组饲养下发育到成年早期。在第 62 天，大鼠被注入载体、CRF（1）受体拮抗剂 antalarmin（0.25-0.5μg）或 CRF（2）受体拮抗剂 antisauvagine-30（2μg）到背侧中缝核，在引入高架十字迷宫前 20 分钟。与分组饲养的大鼠相比，隔离饲养的大鼠表现出减少的开放臂行为，证实了断奶后社交隔离的焦虑作用。与分组饲养的大鼠相比，将 CRF（2）受体拮抗剂而非 CRF（1）受体拮抗剂注入隔离饲养的大鼠的背侧中缝核，增加了开放臂行为。总体而言，这些发现表明，背侧中缝核中的 CRF（2）受体介导了断奶后社交隔离后的焦虑样状态，并且 CRF（2）受体可能是治疗早期生活应激后焦虑障碍的重要靶点。
