Vocalization as a novel endpoint of atypical attachment behavior in 2,3,7,8-tetrachlorodibenzo-p-dioxin-exposed infant mice

Eiki Kimura, Chiharu Tohyama

Mammalian attachment behaviors, such as crying, are essential for infant survival by receiving food, protection, and warmth from caregivers. Ultrasonic vocalization (USV) of infant rodents functions to promote maternal proximity. Impaired USV emission has been reported in mouse models of autism spectrum disorder, suggesting that USV is associated with higher brain function. In utero and lactational dioxin exposure is known to induce higher brain function abnormalities in adulthood; however, whether perinatal dioxin exposure affects behavior during infancy is unclear. Therefore, we studied the impact of dioxin exposure on USV emission in infant mice born to dams treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 0.6 or 3.0 µg/kg) on gestational day 12.5. On postnatal days 3-9, USVs of the offspring were recorded for 1 min using a microphone in a sound-attenuated chamber. The total USV and mean call durations in infant mice exposed to 3.0 µg/kg, but not 0.6 µg/kg, were shorter than those in the control mice. In addition, the percentages of complicated call types (i.e., chevron and wave) in mice exposed to 3.0 µg/kg were decreased. Dioxin-induced gene expression changes occurred in the brains of mice exposed to 3.0 µg/kg; however, body weight, motor activity, and vocal fold structure were not significantly affected. These results suggest that infant USV is a useful behavioral endpoint in developmental neurotoxicity assessment that may be used to evaluate effects of chemical exposure on the infant-caregiver interaction.