Corticotropin-releasing factor modulates maternal separation-induced ultrasonic vocalization in rat pups via activation of CRF1 receptor

An infant animal isolated from its mother emits vocalizations spanning from the audible to the ultrasonic. These vocalizations are believed to represent distress signals from the pup. However, the neurobiological basis for vocalizations elicited by isolation has not been well characterized under different environmental conditions. The present study was designed to clarify the role of the corticotropin-releasing factor (CRF) system in vocalizations elicited by isolating a rat pup at ambient temperatures of 37 °C (temperature of the nest in which the mother and littermates are present) and 24 °C (room temperature). Sprague-Dawley rat pups at 7 days old were isolated from their dam, then the number of vocalizations was measured for 5 min. The number of vocalizations increased when ambient temperature was changed from 37 °C to 24 °C. Systemic administration of CRF (3 or 10 mg/kg) increased the number of vocalizations at 37 °C in a dose-dependent manner. CRF-induced increases in the number of vocalizations at 3 mg/kg were completely blocked by a selective CRF1 receptor antagonist, NBI27914 (3 mg/kg), but not by a selective CRF2 receptor antagonist, K41498 (3 mg/kg). NBI27914 (30 mg/kg), but not K41498 (3 mg/kg), suppressed the increased number of vocalizations at 24 °C. These results demonstrate involvement of the CRF-CRF1 receptor regulatory system on the modulation of ultrasonic vocalizations by rat pups separated from their dam.