Lallai Valeria, Congiu Cristina, Craig Giulia, Manca Letizia, Chen Yen-Chu, Dukes Angeline J, Fowler Christie D, Dazzi Laura
Department of Neurobiology and Behavior, University of California Irvine, Irvine, CA, 92697, USA.
Department of Life and Environmental Sciences, Section of Neuroscience and Anthropology, Centre of Excellence for the Neurobiology of Dependence, University of Cagliari, 09042, Monserrato, CA, Italy.
Neurobiol Stress. 2024 Mar 2;30:100620. doi: 10.1016/j.ynstr.2024.100620. eCollection 2024 May.
Early development is characterized by dynamic transitions in brain maturation, which may be impacted by environmental factors. Here, we sought to determine the effects of social isolation from postweaning and during adolescence on reward behavior and dopaminergic signaling in male rats. Subjects were socially isolated or group housed at postnatal day 21. Three weeks later, extracellular dopamine concentrations were examined in the medial prefrontal cortex (mPFC) and nucleus accumbens shell (NAc) during a feeding bout. Surprisingly, opposing effects were found in which increased mPFC dopamine concentrations were observed in group housed, but not isolated, rats. In stark contrast, increased dopamine levels were found in the NAc of isolated, but not group housed, rats. Moreover, the absence of an effect in the mPFC of the isolated rats could not be reversed by subsequent group housing, demonstrating the remarkable long-term effects on dopamine signaling dynamics. When provided a highly palatable food, the isolated subjects exhibited a dramatic increase in mPFC dopamine levels when the chocolate was novel, but no effects following chronic chocolate consumption. In contrast, the group housed subjects showed significantly increased dopamine levels only with chronic chocolate consumption. The dopamine changes were correlated with differences in behavioral measures. Importantly, the deficit in reward-related behavior during isolation could be reversed by microinjection of either dopamine or cocaine into the mPFC. Together, these data provide evidence that social isolation from postweaning and during adolescence alters reward-induced dopamine levels in a brain region-specific manner, which has important functional implications for reward-related behavior.
早期发育的特点是大脑成熟过程中的动态转变，这可能会受到环境因素的影响。在此，我们试图确定断奶后及青春期社会隔离对雄性大鼠奖励行为和多巴胺能信号传导的影响。实验对象在出生后第21天被进行社会隔离或群居饲养。三周后，在进食期间检测内侧前额叶皮质（mPFC）和伏隔核壳（NAc）中的细胞外多巴胺浓度。令人惊讶的是，发现了相反的效应，即群居而非隔离饲养的大鼠中mPFC多巴胺浓度升高。与之形成鲜明对比的是，隔离而非群居饲养的大鼠的NAc中多巴胺水平升高。此外，隔离大鼠mPFC中缺乏效应的情况不能通过随后的群居饲养来逆转，这表明对多巴胺信号动态具有显著的长期影响。当提供高度可口的食物时，隔离的实验对象在巧克力新颖时mPFC多巴胺水平急剧增加，但长期食用巧克力后则无影响。相比之下，群居的实验对象仅在长期食用巧克力时多巴胺水平显著增加。多巴胺的变化与行为测量的差异相关。重要的是，隔离期间奖励相关行为的缺陷可通过向mPFC微量注射多巴胺或可卡因来逆转。总之，这些数据提供了证据，表明断奶后及青春期的社会隔离以脑区特异性方式改变奖励诱导的多巴胺水平，这对奖励相关行为具有重要的功能意义。
