De Michelis Mograbi Karla, Okeowo Oritoke Modupe, Sumaran Paula, Dale Camila Squarzoni, de Carvalho Milene Cristina, Covolan Luciene, Hamani Clement, Suchecki Deborah
Department of Physiology, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
Department of Physiology, School of Basic Medical Sciences, College of Health Sciences, Federal University of Technology, Akure, Nigeria.
Mol Neurobiol. 2025 Nov 11;63(1):26. doi: 10.1007/s12035-025-05375-6.
Exposure to unpredictable chronic stress has a significant impact on physical and mental health. We have previously reported that a chronic unpredictable movement restraint (CUMR) paradigm increased immobility in the forced swim test and hippocampal pro-inflammatory cytokines. In the present study, we assessed CUMR impact on social motivation and neurobiological underpinnings. Adult male rats were grouped as either control or CUMR and subjected to 2, 4, or 6 h of restraint/day for 3 weeks. Thereafter, social behaviours (social investigation and social interaction) and synaptophysin, serotonin, and dopamine levels were assessed in several brain areas. We found that CUMR-exposed animals displayed reduced body weight gain, less investigation of an unknown rat, and increased dominant behaviour. In addition, CUMR exposure reduced serotonin levels in the hippocampus and augmented dopamine levels in the amygdala and hypothalamus and serotonin turnover in the amygdala than non-stressed rats. Hippocampal serotonin was positively correlated, whereas serotonin levels in the amygdala were negatively correlated with social behaviour. Dominant behaviour was positively correlated with dopamine levels in the hypothalamus. These results indicate that CUMR impairs social behaviour, which may be explained by changes in serotonin and dopamine levels in specific brain areas.
暴露于不可预测的慢性应激对身心健康有重大影响。我们之前报道过，慢性不可预测运动限制（CUMR）范式增加了强迫游泳试验中的不动时间以及海马促炎细胞因子。在本研究中，我们评估了CUMR对社交动机和神经生物学基础的影响。成年雄性大鼠被分为对照组或CUMR组，每天进行2、4或6小时的限制，持续3周。此后，在几个脑区评估社交行为（社交探究和社交互动）以及突触素、血清素和多巴胺水平。我们发现，暴露于CUMR的动物体重增加减少，对陌生大鼠的探究减少，且优势行为增加。此外，与未受应激的大鼠相比，CUMR暴露降低了海马中的血清素水平，增加了杏仁核和下丘脑的多巴胺水平以及杏仁核中的血清素周转率。海马血清素呈正相关，而杏仁核中的血清素水平与社交行为呈负相关。优势行为与下丘脑多巴胺水平呈正相关。这些结果表明，CUMR损害社交行为，这可能由特定脑区血清素和多巴胺水平的变化来解释。
