Effects of corticotropin-releasing hormone on distress vocalizations and locomotion in maternally separated mouse pups

Abstract

The behavioral effects of corticotropin-releasing hormone (CRH) appear to depend on the baseline state of arousal of the animal. In this study, this hypothesis was tested using a 4-min maternal separation procedure in 7-day-old male and female mouse pups (outbred CFW strain). Two intensities of stress were used to assess the effects of intracerebroventricularly administered r/hCRH: a mild stress condition where the ambient temperature was close to nest temperature (30 °C) and rates of maternal separation-induced ultrasonic vocalizations (USVs) were relatively low (ca. 25/4 min), and a more stressful condition where the temperature was 19 °C and the rates of USVs were high (ca. 250/4 min). Differential effects of CRH on vocalization rate and locomotor behavior were observed to be dependent on the level of stress. In the more stressful 19 °C condition, r/hCRH dose-dependently reduced the number of USVs without affecting motor behavior, as indexed by grid crossings. In contrast, in the 30 °C condition, only the highest dose of r/hCRH reduced calling while r/hCRH activated motor behavior over a wider range of doses. These effects were independent of hypothalamus–pituitary–adrenal (HPA) axis activity, as measured by plasma corticosterone levels. The present study indicates that in mouse pups, the effects of CRH administration depend on baseline levels of arousal and that the behavioral effects of CRH administration can be dissociated under mild and more stressful conditions.