Being cautious of unfamiliar conspecifics is adaptive because sick or aggressive conspecifics may jeopardize survival and well-being. However, prolonged or excessive caution, i.e. fear related to social situations, is maladaptive and may result in social anxiety disorder. Some anxiety disorders in humans are associated with polymorphisms of the neuropeptide S receptor (NPSR) gene. In line with this finding, animal studies showed an important role of NPS and NPSR in anxiety and fear. The present study investigated the role of NPSR deficiency in social behavior under non-aversive and aversive conditions. For this, female and male NPSR-deficient mice were tested for (1) sociability and social novelty and (2) acquisition, expression, and extinction of conditioned social fear. The present study revealed very particular effects of the NPSR genotype: Sociability was reduced in female heterozygous NPSR-deficient mice, but was unaffected in males and the other genotypes. Furthermore, the NPSR genotype did not affect the acquisition and expression of conditioned social fear, but its extinction was impaired in heterozygous and facilitated in homozygous NPSR-deficient mice. This indicates that the NPS system plays a role in social behavior under non-aversive and aversive conditions, partly in a sex-dependent manner. The present findings may help to explain social symptoms in anxiety disorders associated with the NPSR genotype.

对不熟悉的同种动物保持谨慎是适应性的，因为生病或具有攻击性的同种动物可能会危及生存和福祉。然而，长期或过度谨慎，即与社交场合相关的恐惧，是适应不良的，可能导致社交焦虑症。人类的一些焦虑症与神经肽 S 受体 (NPSR) 基因的多态性有关。与这一发现一致，动物研究表明 NPS 和 NPSR 在焦虑和恐惧中起着重要作用。本研究调查了 NPSR 缺陷在非厌恶和厌恶条件下的社会行为中的作用。为此，对雌性和雄性 NPSR 缺陷小鼠进行了 (1) 社交性和社会新奇性测试，以及 (2) 条件性社交恐惧的获得、表达和消失。本研究揭示了 NPSR 基因型的非常特殊的影响：雌性杂合 NPSR 缺陷小鼠的社交能力降低，但在雄性和其他基因型小鼠中不受影响。此外，NPSR 基因型不影响条件性社交恐惧的获得和表达，但其灭绝在杂合子中受损，并在纯合 NPSR 缺陷小鼠中得到促进。这表明 NPS 系统在非厌恶和厌恶条件下的社会行为中发挥作用，部分以性别依赖的方式。目前的发现可能有助于解释与 NPSR 基因型相关的焦虑症的社会症状。但它的灭绝在杂合子中受损，在纯合子 NPSR 缺陷小鼠中得到促进。这表明 NPS 系统在非厌恶和厌恶条件下的社会行为中发挥作用，部分以性别依赖的方式。目前的发现可能有助于解释与 NPSR 基因型相关的焦虑症的社会症状。但它的灭绝在杂合子中受损，在纯合子 NPSR 缺陷小鼠中得到促进。这表明 NPS 系统在非厌恶和厌恶条件下的社会行为中发挥作用，部分以性别依赖的方式。目前的发现可能有助于解释与 NPSR 基因型相关的焦虑症的社会症状。