Sex differences in ultrasonic vocalization and hormonal stress response of an anxious mice strain during the early postnatal period

Abstract

Development of anxiolytics requires animal models; therefore anxious (AX) and nonanxious (nAX) mice have been selectively bred based upon their adult behaviour in reaction to handling. Since inadequate response to postnatal challenges may have lifelong consequences, we aimed to determine whether alterations in postnatal stress-coping may contribute to the state of anxiety in adult AX mice. Maternal separation-induced ultrasonic vocalization (MS-USV) was studied in one-week-old nAX-AX mice and one week later the endocrine stress response was measured after lipopolysaccharide (LPS) stimulation, a model of bacterial infection, with special focus on sex differences. It was established that AX females produced a significantly lower frequency and duration of MS-USV than nAX female mice. USV emitted by AX males showed only a tendency to be reduced compared to nAX males. LPS injection generated a significantly increased adrenocorticotropin release in nAX mice only and with no sex-related difference observed. Resting corticosterone levels were higher in AX mice compared to nAX, however, this difference reached the level of significance only in females. LPS-injection was able to induce significant corticosterone elevation with markedly higher levels in AX females than nAX females. To sum up, we conclude that females are more susceptible to the influence of stressors during the early postnatal period, as they exhibited more pronounced reactions. The adult state anxiety of the strain was not paralleled by MS-USV during the perinatal period. Thus, the question arises if MS-USV indeed reflects anxiety only. According to our expectation, AX animals had higher baseline stress-hormone levels, but their reactivity to stressors was altered, which may have contributed to their supposed adult phenotype.