Wang Sheng-Chiang, Lin Chen-Cheng, Chen Chun-Chuan, Liu Yia-Ping
Department of Psychiatry, School of Medicine, National Defense Medical Center, 114 Taipei.
Department of Psychiatry, Tri-Service General Hospital Songshan Branch, 105 Taipei.
J Integr Neurosci. 2025 Apr 3;24(4):33400. doi: 10.31083/JIN33400.
Stress is a critical determinant of social behavior, with oxytocin playing a key role in buffering stress effects and facilitating social bonding. However, the relationship between stress-induced fear and oxytocin-associated sociability remains unclear, particularly in contexts reminiscent of prior stress. This study investigates whether acute restraint stress (ARS) alters anxiety-related behaviors and prosocial choices, and whether these effects can be modulated by pharmacological intervention targeting the oxytocin and corticotropin-releasing hormone (CRH) systems.
Sprague-Dawley rats were subjected to ARS and assessed for anxiety-like behavior using the elevated T-maze (ETM) and for prosocial behavior using the social choice test (SCT). The effects of the oxytocin receptor antagonist L-368899 and CRH receptor antagonist antalarmin were evaluated in this paradigm. Plasma corticosterone was checked peripherally and the tissue concentrations of serotonin (5-HT), dopamine (DA), and norepinephrine (NE) were measured in the hippocampus, medial prefrontal cortex (mPFC), and amygdala to assess stress-related neurochemical changes in the fear circuit.
(i) ARS rats showed a significant increase in prosocial preference compared to control, an effect blocked by L-368899 or antalarmin. (ii) ARS rats exhibited reduced corticosterone levels, together with shorter avoidance latency, and longer escape latency in the ETM. (iii) Neurochemically, ARS rats had decreased DA and increased NE levels in the mPFC, both of which were normalized by L-368899 treatment.
Oxytocin modulates stress-induced alterations in monoaminergic activity within the mPFC, influencing social choice behavior. These findings provide new insights into the neurobiological mechanisms underlying stress-related sociability and the context-dependent role of oxytocin in fear memory and social behavior.
应激是社会行为的关键决定因素，其中催产素在缓冲应激影响和促进社会联系方面发挥着关键作用。然而，应激诱导的恐惧与催产素相关的社交能力之间的关系仍不清楚，尤其是在让人想起既往应激的情境中。本研究调查急性束缚应激（ARS）是否会改变焦虑相关行为和亲社会选择，以及这些效应是否可通过针对催产素和促肾上腺皮质激素释放激素（CRH）系统的药物干预来调节。
将斯普拉格-道利大鼠进行急性束缚应激处理，并使用高架T迷宫（ETM）评估其焦虑样行为，使用社会选择测试（SCT）评估其亲社会行为。在此范式中评估了催产素受体拮抗剂L-368899和CRH受体拮抗剂安他拉美（antalarmin）的作用。外周检查血浆皮质酮，并测量海马、内侧前额叶皮质（mPFC）和杏仁核中血清素（5-HT）、多巴胺（DA）和去甲肾上腺素（NE）的组织浓度，以评估恐惧回路中与应激相关的神经化学变化。
（i）与对照组相比，急性束缚应激大鼠的亲社会偏好显著增加，这一效应被L-368899或安他拉美阻断。（ii）急性束缚应激大鼠的皮质酮水平降低，同时在高架T迷宫中的回避潜伏期缩短，逃避潜伏期延长。（iii）在神经化学方面，急性束缚应激大鼠内侧前额叶皮质中的多巴胺水平降低，去甲肾上腺素水平升高，而这两者经L-368899治疗后均恢复正常。
催产素调节内侧前额叶皮质内应激诱导的单胺能活动变化，影响社会选择行为。这些发现为应激相关社交能力的神经生物学机制以及催产素在恐惧记忆和社会行为中依赖情境的作用提供了新的见解。
