Evaluation of ultrasonic vocalizations in a neurodevelopmental model of schizophrenia during the early life stages of rats

In an animal neurodevelopmental model of schizophrenia, we investigated ultrasonic communication and social behavior in male and female rats. Pregnant dams were treated with methylazoxymethanol acetate (MAM; 22 mg/kg) at 17 days of gestation. First, we examined the ultrasonic vocalizations (USVs) emitted by 8-day-old pups isolated from their mothers and placed in a familiar or an unfamiliar environment. Second, we assessed tickling-induced USVs, social play (SP) behavior and accompanying USVs in 30-day-old juveniles. Independent of the prenatal treatment, sex differences were noted at both ages. In the pups isolated from their mothers, compared to the females, the males produced flatter calls with a lower frequency. Compared to the females, the tickling-induced male USVs were characterized by a higher frequency, and the male SP-induced USVs showed a broader bandwidth and more modulated structure. Additionally, the numbers of both SP-induced USVs and SP episodes in the males were higher than those in the females. In contrast, the MAM exposure reduced the ultrasonic communication and social behavior independent of age almost equally in the male and female rats. The MAM-exposed isolated pups and juveniles experiencing tickling and social interaction displayed lower USV bandwidths, suggesting that the complexity of their ultrasonic communication was reduced. In addition, the MAM-exposed juveniles demonstrated a lower number of 50-kHz happy calls and decreased SP duration, which is suggestive of social withdrawal or negative-like symptoms. These data demonstrate that young MAM-exposed rats display an atypical repertoire of USVs and reduced play behavior suggestive of communication deficits associated with schizophrenia.