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Objectives Autism spectrum disorders (ASDs) have core impairments in social communication as well as the presence of repetitive, stereotypic behaviors and restricted interests. Older adolescents and young adults are particularly impacted by these deficits. Preclinical data implicate glutamatergic dysfunction in the pathophysiology of ASDs. D-Cycloserine (DCS), a partial glycineB agonist at the N-methyl-D-aspartic acid receptor site, has been shown to improve sociability in mouse models and a small human study. The sensitivity of the obligatory glycineB co-agonist binding site may change with daily administration of DCS as a result of agonist-induced desensitization. The efficacy of a “pulsed” once-weekly administration versus “daily” administration of DCS was compared. Methods Males and females, ages 14 to 25 years, with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision diagnosis of an ASD were enrolled in a double-blind, randomized 10-week trial consisting of 8 weeks of active drug with either weekly or daily administration of 50 mg of DCS followed by a 2-week follow-up visit. Results For the purposes of this study, no statistical or clinical differences existed between the 2 dosage groups on the Aberrant Behavior Checklist subscale 3, which measures stereotypies/repetitive movements. When combining groups, a statistically significant decrease of 37% was found from baseline to week 8 when study drug was completed using a linear mixed effects model (P = 0.003). Conclusions D-Cycloserine was shown to be effective in improving stereotypic symptoms in older adolescents and young adults with ASDs measured by the Aberrant Behavior Checklist subscale 3. In addition, DCS was safe and well tolerated.

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The Balb/c mouse is proposed as a model of human disorders with prominent deficits of sociability, such as autism spectrum disorders (ASDs) that may involve pathophysiological disruption of NMDA receptor-mediated neurotransmission. A standard procedure was used to measure sociability in 8-week-old male genetically inbred Balb/c and outbred Swiss Webster mice. Moreover, because impaired sociability may influence the social behavior of stimulus mice, we also measured the proportion of total episodes of social approach made by the stimulus mouse while test and stimulus mice were allowed to interact freely. Three raters with good inter-rater agreement evaluated operationally defined measures of sociability chosen because of their descriptive similarity to deficits of social behavior reported in persons with ASDs. The data support previous reports that the Balb/c mouse is a genetic mouse model of impaired sociability. The data also show that the behavior of the social stimulus mouse is influenced by the impaired sociability of the Balb/c strain. Interestingly, operationally defined measures of sociability did not necessarily correlate with each other within mouse strain and the profile of correlated measures differed between strains. Finally, "stereotypic" behaviors (i.e. rearing, grooming and wall climbing) recorded during the session of free interaction between the test and social stimulus mice were more intensely displayed by Swiss Webster than Balb/c mice, suggesting that the domains of sociability and "restricted repetitive and stereotyped patterns of behavior" are independent of each other in the Balb/c strain.

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