D-cycloserine improves sociability and spontaneous stereotypic behaviors in 4-week old mice

Abstract

Balb/c mice are a model of impaired sociability and social motivation relevant to autism spectrum disorders (ASDs). Impaired sociability of 8-week old Balb/c mice is attenuated by agonists of the glycineB site on the NMDA receptor, such as d-cycloserine. Although ASDs are often recognized in toddlerhood, there is interest in earlier identification (e.g., before 6months) and disease-modifying interventions to improve functional outcomes. Thus, we wondered if d-cycloserine could improve sociability in 4-week old Balb/c mice, similar to its effects in 8-week old mice. d-Cycloserine improved measures of impaired sociability in 4-week old (i.e., one-week post-weanling) Balb/c mice. Moreover, because stereotypies can compete with the salience of social stimuli, we compared Balb/c and Swiss Webster mice on several spontaneous stereotypic behaviors emerging during social interaction with a social stimulus mouse. Interestingly, similar to 8-week old mice, spontaneous stereotypic behaviors during social interaction were more intense in the 4-week old Swiss Webster mice; furthermore, d-cycloserine reduced their intensity. Thus, d-cycloserine improves both sociability and stereotypic behaviors, but these effects may lack strain-selectivity. A prosocial effect of d-cycloserine was observed at a dose as low as 32.0mg/kg in Balb/c mice. d-cycloserine has the therapeutic properties of a desired medication for ASDs; specifically, a medication should not improve stereotypic behaviors at the expense of worsening sociability and vice versa. The data suggest that targeting the NMDA receptor can have promising therapeutic effects on two prominent domains of psychopathology in ASDs: impaired sociability and spontaneous stereotypic behaviors.