EMOTIONAL BLUNTING IN RATS: CENTRAL SEROTONIN DEFICIENCY REDUCES SOCIO-AFFECTIVE ULTRASONIC VOCALIZATIONS ACROSS EMOTIONAL VALENCES

Serotonin (5-HT) is a major neurotransmitter whose disrupted signaling is linked to neuropsychiatric disorders such as autism and anxiety, both marked by deficits in socio-affective social communication and emotion regulation. Rats are valuable models for such disorders due to their complex social and emotional behaviors, including socio-affective communication via ultrasonic vocalizations (USV). Juvenile and adult rats emit aversive 22-kHz-USV in threatening situations (e.g., fear learning) and appetitive 50-kHz-USV during positive experiences (e.g., social play). To study 5-HT’s role in socio-affective USV across emotional valences, we employed a rat model lacking central 5-HT from a deficiency of tryptophan-hydroxylase-2 (Tph2), the key enzyme for brain 5-HT synthesis. We tested 84 rats using a comprehensive behavioral battery with simultaneous 22-kHz and 50-kHz-USV recording. Behavioral phenotypes of homozygous Tph2^-/- and heterozygous Tph2^+/- rats were compared with wildtype Tph2^+/+ controls of both sexes throughout development. Tph2^-/- rats showed altered social play -especially increased mounting- with changes in 50-kHz-USV, most notably missing the anticipatory increase over three consecutive play sessions. Furthermore, the social approach to playback of pro-social 50-kHz-USV was delayed. During auditory fear conditioning (CS: tone, US: foot-shock), freezing was unchanged, but 22-kHz-USV were greatly reduced. These changes correlated with lower anxiety-related behavior and less exploration in elevated-plus-maze and open-field tests, respectively. Our findings indicate central 5-HT deficiency causes deficits in socio-affective USV, suggesting emotional blunting.