Department of Pharmacology and Toxicology, Pharmacy School, University of Kansas, Lawrence, KS, USA.
Department of Pharmacology and Toxicology, Pharmacy School, University of Kansas, Lawrence, KS, USA.
Neuropharmacology. 2021 Oct 15;198:108770. doi: 10.1016/j.neuropharm.2021.108770. Epub 2021 Aug 28.
Social anxiety disorder (SAD) is a prevalent mental illness in both men and women, but current treatment approaches with selective serotonin reuptake inhibitors (SSRI) have limited success. The neuropeptide oxytocin (OXT) has become a therapeutic target due to its prosocial and anxiolytic effects. Nevertheless, no research has focused on the impact of chronic OXT treatment in animal models of SAD. Social defeat stress is an animal model of social conflict that reliably induces a social avoidance phenotype, reflecting symptoms observed in individuals suffering from SAD. Here, we used the socially monogamous prairie vole, which exhibits aggressive behavior in both sexes, to examine the effects of OXT and SSRI treatment following social defeat stress in males and females. Defeated voles became avoidant in unfamiliar social situations as early as one day after defeat experience, and this phenotype persisted for at least eight weeks. OXT receptor (OXTR) binding in mesocorticolimbic and paralimbic regions was reduced in defeated females during the eight-week recovery period. In males, serotonin 1A receptor binding was decreased in the basolateral amygdala and dorsal raphe nucleus starting at one week and four weeks post-defeat, respectively. Chronic intranasal treatment with OXT had a negative effect on sociability and mesolimbic OXTR binding in non-defeated females. However, chronic intranasal OXT promoted social engagement and increased mesolimbic OXTR binding in defeated females but not males. SSRI treatment led to only modest effects. This study identifies a sex-specific and stress-dependent function of intranasal OXT on mesolimbic OXTR and social behaviors.
社交焦虑障碍（SAD）是一种在男性和女性中普遍存在的精神疾病，但目前使用选择性 5-羟色胺再摄取抑制剂（SSRI）的治疗方法收效甚微。神经肽催产素（OXT）因其具有亲社会和抗焦虑作用而成为治疗靶点。然而，目前还没有研究关注慢性 OXT 治疗对 SAD 动物模型的影响。社交挫败应激是一种社会冲突的动物模型，可可靠地诱导出回避社会的表型，反映了患有 SAD 的个体的症状。在这里，我们使用社会一夫一妻制的草原田鼠，它们在两性中都表现出攻击性行为，来研究 OXT 和 SSRI 治疗对雄性和雌性田鼠在社交挫败应激后的影响。挫败的田鼠在遭受挫败后的一天内就会对陌生的社交环境表现出回避行为，并且这种表型至少持续八周。在八周的恢复期内，雌性战败者的中脑边缘和边缘旁区域的 OXT 受体（OXTR）结合减少。在雄性中，5-羟色胺 1A 受体结合在基底外侧杏仁核和背侧中缝核中分别在挫败后一周和四周开始减少。慢性鼻内 OXT 治疗对未被击败的雌性的社交能力和中脑边缘 OXTR 结合有负面影响。然而，慢性鼻内 OXT 促进了被击败的雌性的社交参与，并增加了中脑边缘 OXTR 的结合，但对雄性没有影响。SSRI 治疗仅产生适度的效果。这项研究确定了鼻内 OXT 对中脑边缘 OXTR 和社交行为的性别特异性和应激依赖性作用。
