Ultrasonic vocalizations (USV) serve important communicative functions as socio-affective signals in rats. In aversive situations, such as inter-male aggression and predator exposure, 22-kHz USV are emitted. They likely function as appeasement signals during fighting and/or as alarm calls to warn conspecifics. In appetitive situations, 50-kHz USV are uttered, most notably during social interactions, such as rough-and-tumble play and mating. It is believed that they fulfill an affiliative function as social contact calls. Social experiences or their lack, such as social isolation, can have profound impact on the emission of 22- and 50-kHz USV by the sender in later life, albeit direction and strength of observed effects vary, with time point of occurrence and duration being critical determinants. Little, however, is known about how social experiences affect the behavioral responses evoked by 22- and 50-kHz USV in the recipient. By means of our 50-kHz USV radial maze playback paradigm, we recently showed that the behavioral response elicited in the recipient is affected by post-weaning social isolation. Rats exposed to four weeks of isolation during the rough-and-tumble play period did not display social approach behavior toward 50-kHz USV but some signs of social avoidance. We further found that physical environmental enrichment providing minimal opportunities for social interactions has similar detrimental effects. Together, this indicates that social experiences can affect socio-affective communication in rodents, both at the level of sender and recipient. Deficits seen following post-weaning social isolation or physical environmental enrichment might be useful to model aspects of neurodevelopmental disorders characterized by social and communication deficits, such as autism and schizophrenia.