Oxytocin is currently being considered as a novel therapeutic for anxiety disorders due to its ability to promote affiliative behaviors. In the nucleus accumbens (NAc) activation of oxytocin receptors (OTR) promotes social approach (time spent near an unfamiliar individual). Here, we show that stressful social experiences reduce the expression of NAc OTR mRNA, coinciding with decreases in social approach. Social stressors also increase social vigilance, characterized as orienting to an unfamiliar individual without approaching. Vigilance is a key component of behavioral inhibition, a personality trait that is a risk factor for anxiety disorders. To understand whether NAc OTR can modulate both social approach and vigilance, we use pharmacological approaches to assess the impact of activation or inhibition of NAc OTR downstream pathways on these behaviors. First, we show that in unstressed male and female California mice, inhibition of OTR by an unbiased antagonist (L-368,899) reduces social approach but does not induce social vigilance. Next, we show that infusion of Atosiban, an OTR-Gq antagonist/OTR-Gi agonist, has the same effect in unstressed females. Finally, we show that Carbetocin, a biased OTR-Gq agonist, increases social approach in stressed females while simultaneously inhibiting social vigilance. Taken together these data suggest that OTR in the NAc differentially modulate social approach and social vigilance, primarily through an OTR-Gq mechanism. Importantly, pharmacological inhibition of OTR alone is insufficient to induce vigilance in unstressed mice, suggesting that mechanisms modulating social approach may be distinct from mechanisms modulating social vigilance.

催产素目前被认为是一种治疗焦虑症的新型疗法，因为它能够促进从属行为。在伏隔核 (NAc) 中，催产素受体 (OTR) 的激活促进了社交方式（在不熟悉的人附近度过的时间）。在这里，我们表明压力的社交经历会降低 NAc OTR mRNA 的表达，与社交方式的减少相吻合。社会压力源也增加了社会警惕性，其特点是在不接近的情况下定向到一个不熟悉的人。警惕是行为抑制的关键组成部分，行为抑制是一种人格特征，是焦虑症的危险因素。为了了解 NAc OTR 是否可以调节社交方式和警惕性，我们使用药理学方法来评估 NAc OTR 下游通路的激活或抑制对这些行为的影响。首先，我们表明，在无压力的雄性和雌性加利福尼亚小鼠中，无偏见的拮抗剂 (L-368,899) 对 OTR 的抑制会降低社交方式，但不会引起社交警惕。接下来，我们表明输注阿托西班（一种 OTR-Gq 拮抗剂/OTR-Gi 激动剂）在无压力的女性中具有相同的效果。最后，我们发现 Carbetocin 是一种有偏见的 OTR-Gq 激动剂，它增加了压力女性的社交方式，同时抑制了社交警惕性。综合这些数据表明，NAc 中的 OTR 主要通过 OTR-Gq 机制差异调节社会方法和社会警惕性。重要的是，仅对 OTR 的药理学抑制不足以引起无应激小鼠的警觉，