Oxytocin (OT) is a critical molecule for social recognition that mediates social and emotional behaviors. OT is released during stress and acts as an anxiolytic factor. To know the precise molecular mechanisms underlying OT release into the brain during stress is important. It has been reported that intracellular concentrations of free calcium in the hypothalamic neurons are elevated by simultaneous stimulation of cyclic ADP-ribose (cADPR) and heat. We have reported in vitro and in vivo data that supports the idea that release of OT in the brain of male mice is regulated by cADPR and fever in relation to stress conditions. 1) Significantly higher levels of OT release were observed in hypothalamus cultures isolated from subordinate mice in group-housed males compared to dominant males after cage-switch stress; 2) OT concentrations in micro-perfusates at the paraventricular nucleus upon perfusion stimulation with cADPR were enhanced in subordinate mice compared to dominant mice; 3) The OT concentration in the cerebrospinal fluid (CSF) was higher in endotoxin-shock mice with fever compared to controls with no body temperature increase; and 4) In mice exposed to new environmental stress, the CSF OT level transiently increased 5 min after exposure, while the rectal temperature increased from 36.6 °C to 37.8 °C from 5 to 15 min after exposure. In this review, we examine whether or not cADPR and hyperthermia co-regulate hypothalamic OT secretion during social stress through the elevation of intracellular free Ca²⁺ concentrations involved in CD38-dependent Ca²⁺ mobilization and TRPM2-dependent Ca²⁺ influx. Finally, we propose that the interaction between CD38 and TRPM2 seems to be a new mechanism for stress-induced release of OT, which may result in anxiolytic effects for temporal recovery from social impairments in children with autism spectrum disorder during hyperthermia.

催产素（OT）是介导社交和情感行为的社会认可的关键分子。OT在压力下释放，并作为抗焦虑因子。知道在压力下OT释放到大脑中的确切分子机制很重要。据报道，通过同时刺激环状ADP-核糖（cADPR）和加热，下丘脑神经元中细胞内游离钙的浓度升高。我们已经报道了体内和体外数据支持雄性小鼠大脑中OT的释放受应激条件相关的cADPR和发烧的调节。1）与笼型转换后的雄性雄性相比，成群饲养的雄性下丘脑培养物中分离出的下丘脑培养物中的OT释放水平显着高于显性雄性。2）与优势小鼠相比，cADPR灌流刺激后，室旁核微灌流液中的OT浓度升高。3）与无体温升高的对照组相比，发烧内毒素休克小鼠的脑脊髓液（CSF）中的OT浓度更高。和4）在暴露于新的环境压力的小鼠中，暴露后5分钟CSF OT水平瞬时升高，而直肠温度从36.6°C升高至37。暴露后5至15分钟为8°C。在这篇综述中，我们研究了在社会应激过程中，cADPR和热疗是否通过细胞内游离Ca的升高来共同调节下丘脑OT分泌。^{2 +}浓度参与CD38依赖的Ca ²⁺动员和TRPM2依赖的Ca ²⁺涌入。最后，我们认为CD38和TRPM2之间的相互作用似乎是压力诱导的OT释放的一种新机制，这可能会导致自闭症谱系障碍患儿在高温期间从社会障碍中的暂时恢复而产生抗焦虑作用。