Sociability and extinction of conditioned social fear is affected in neuropeptide S receptor-deficient mice.

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.