Early-life risperidone administration alters maternal-offspring interactions and juvenile play fighting

Abstract

Risperidone is an antipsychotic drug that is approved for use in childhood psychiatric disorders such as autism. One concern regarding the use of this drug in pediatric populations is that it may interfere with social interactions that serve to nurture brain development. This study used rats to assess the impact of risperidone administration on maternal-offspring interactions and juvenile play fighting between cage mates. Mixed-sex litters received daily subcutaneous injections of vehicle or 1.0 or 3.0mg/kg of risperidone between postnatal days (PNDs) 14-42. Rats were weaned and housed three per cage on PND 21. In observations made between PNDs 14-17, risperidone significantly suppressed several aspects of maternal-offspring interactions at 1-hour post-injection. At 23 h post-injection, pups administered risperidone had lower activity scores and made fewer non-nursing contacts with their moms. In observations of play-fighting behavior made once a week between PNDs 22-42, risperidone profoundly decreased many forms of social interaction at 1h post-injection. At 23h post-injection, rats administered risperidone made more non-social contacts with their cage mates, but engaged in less social grooming. Risperidone administration to rats at ages analogous to early childhood through adolescence in humans produces a pattern of abnormal social interactions across the day that could impact how such interactions influence brain development.

Keywords: Antipsychotic; Autism; Development; Dopamine; Forebrain; Social behavior.

Fig. 1

Measures of maternal-offspring interactions at 1 and 23 hours post-injection. Data represent means ± s.e.m. A single asterisk indicates a significant difference between the Vehicle group and the Risp 3.0 group at a single post-injection time point. Double asterisks indicate statistically significant differences between the Vehicle group and both the Risp 1.0 and Risp 3.0 groups at a single post-injection time point. There was a trend towards a difference between Vehicle and Risp 1.0 group at 23 hours in a. and e. as indicated by the p values. n = 12 for each group.

Fig. 2

Measures of play-fighting behavior at 23 hours post-injection across three weeks of testing (a.-g.). In h., the data from the three weeks are averaged as a function of sex. Data represent mean total score ± s.e.m. A single asterisk indicates a significant difference between the Vehicle group and the Risp 3.0 group during a given week, except in h. where an asterisk differentiates Vehicle males from Risp 3.0 males and Vehicle females. Double asterisks indicate statistically significant differences between the Vehicle group and both Risp 1.0 and Risp 3.0 groups during a given week. There were trends towards a difference between Vehicle and Risp 3.0 group at PNDs 22-28 in c., and at PNDs 29-35 and PNDs 36-42 in d., as indicated by the p values. In h., there were trends towards lower self-grooming scores in the female rats from the Risp 1.0 and 3.0 groups relative to the males from the Vehicle group. n = 12 for each group, except for h. where n = 6 per group.