Lack of social exploratory activation in male μ-opioid receptor KO mice in response to playback of female ultrasonic vocalizations

Abstract

The opioid system controls social behavior and it was hypothesized that it therefore plays a role in neuropsychiatric disorders such as autism that are characterized by social and communication deficits. Mice communicate via ultrasonic vocalizations. As pups, they produce ultrasonic vocalizations when isolated from dam and littermates. These calls serve an important biological purpose, since they elicit search and retrieval behavior in the mother. Administration of μ-opioid-receptor-agonists diminishes such isolation-induced ultrasonic vocalizations and μ-opioid-receptor knock-out mouse pups (Orpm ^–/–) emit fewer ultrasonic vocalizations during isolation than intact controls (Orpm ^+/+). In adulthood, male and female mice produce ultrasonic vocalizations during social interactions. However, little is known about occurrence and function of ultrasonic vocalizations produced by adult females. Here, we conducted a playback experiment in order to assess whether female ultrasonic vocalizations elicit changes in the recipient's behavior and whether a possible change in behavior is dependent on a functioning opioid system by comparing Orpm ^–/– mice with Orpm ^+/+ controls. Our results showed that female ultrasonic vocalizations elicit exploratory activity in male recipients and that elicitation of exploratory activity in response to female ultrasonic vocalizations is dependent on an intact opioid system, since such a response was not seen in Orpm ^–/– mice. Lack of exploratory activation seen in Orpm ^–/– mice is unlikely due to hearing deficits as shown by an auditory cued fear-conditioning-task. Hence, these findings support the phenotypic relevance of Orpm ^–/– mice for the study of autism.

Keywords:

• Autism
• Social behavior
• Opioid system
• Ultrasonic vocalization
• USV

Acknowledgments

Thanks to Brigitte L. Kieffer for scientific support and providing animals. This work was supported by grants from the Gustav‐Adolf-Lienert-Stiftung Germany (MW) and from Telethon Italy (AM and FRD).