Institute of Brain and Behavioral Sciences, College of Life Sciences, Shaanxi Normal University, Xi'an 710062, China.
Institute of Brain and Behavioral Sciences, College of Life Sciences, Shaanxi Normal University, Xi'an 710062, China.
Brain Res. 2021 Aug 15;1765:147497. doi: 10.1016/j.brainres.2021.147497. Epub 2021 Apr 21.
In the early stage of life, experiencing social isolation can generate long-lasting deleterious effects on behaviors and brain development. However, the effects of chronic social isolation during adolescence on social behaviors and its underlying neurobiological mechanisms remain unclear. The present study found that four weeks of social isolation during adolescence impaired social recognition ability in the three-chamber test and five-trial social recognition test, and increased aggressive-like behaviors, but reduced environmental exploration, as showed in the social interaction test. Chronic social isolation decreased levels of dopamine D2 receptor in the shell of the nucleus accumbens (NAcc) and medial prefrontal cortex. It also reduced TH in the NAcc. Using in vivo fiber photometry, it was also found that isolated mice displayed a reduction in NAcc shell activity upon exploring unfamiliar social stimuli. An injection of a 100 ng dose of the D2R agonist quinpirole into the shell of the NAcc reversed behavioral abnormalities induced by chronic social isolation. These data suggest that the dopamine system is involved in alterations in social behaviors induced by chronic social isolation. This finding sheds light on the mechanism underlying abnormalities in social behavior induced by adolescent chronic social isolation and provides a promising target to treat mental diseases relevant to social isolation.
在生命的早期阶段，经历社交隔离会对行为和大脑发育产生持久的有害影响。然而，青春期慢性社交隔离对社交行为及其潜在的神经生物学机制的影响尚不清楚。本研究发现，青春期四周的社交隔离会损害三箱测试和五次社交识别测试中的社交识别能力，并增加类似攻击的行为，但减少环境探索，如社交互动测试所示。慢性社交隔离会降低伏隔核（NAcc）壳和内侧前额叶皮层中的多巴胺 D2 受体水平。它还降低了 NAcc 中的 TH。通过体内光纤光度测定法，还发现隔离小鼠在探索不熟悉的社交刺激时，NAcc 壳活动减少。将 100ng 剂量的 D2R 激动剂喹吡罗注入 NAcc 壳中，可逆转慢性社交隔离引起的行为异常。这些数据表明，多巴胺系统参与了慢性社交隔离引起的社交行为改变。这一发现为青少年慢性社交隔离引起的社交行为异常的机制提供了启示，并为治疗与社交隔离相关的精神疾病提供了有前途的靶点。
