Fluoxetine but not Risperidone Increases Sociability in the BTBR Mouse Model of Autism

In the absence of consistent, certain biomarkers, diagnosis of autism is based on well defined core behavioral symptoms: abnormal social interactions and social communication, and repetitive behaviors and/or restricted interests. Many drugs, including fluoxetine and risperidone, have been used to treat symptoms associated with autism. Risperidone, an atypical antipsychotic that blocks D2 and 5HT2A receptors, has been approved by the United States Food and Drug Administration (FDA) to reduce the repetitive behavior and self-injurious behavior in children with autism. Fluoxetine, a selective serotonin-reuptake inhibitor (SSRI), is being evaluated by the FDA for anxiety and repetitive behaviors in autistic individuals. Serotonin dysregulation is one theory for the etiology of autism (reviewed by Pardo and Eberhart, 2007) and has been linked with comorbid behaviors associated with autism such as depression, anxiety, mood, impulsivity and aggression (reviewed by Soorya et al., 2008; West et al., 2009). Both risperidone and fluoxetine act in the serotonin system. Risperidone antagonizes the serotonin 2A receptor and fluoxetine blocks the serotonin transporter increasing the amount of serotonin available in the synapse.

Animal models are a useful tool in the search for pharmacological treatment for the core symptoms of autism. One approach is to select inbred strains of mice that demonstrate behavioral characteristics that have face validity for autism. The social approach test has been developed to identify deficits in social interaction where a subject mouse has the choice between a social and non-social environment (Moy et al. 2004; Nadler et al. 2004; Moy et al. 2007; Yang et al. 2007; McFarlane et al. 2008; Moy et al. 2008...

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... Brunssen, and J. Waldrop, Review of the evidence for treatment of children with autism with selective serotonin reuptake inhibitors, Journal for Specialists in Pediatric Nursing 14(3) (2009), pp. 183-191. doi:10.1111/j.1744-6155.2009.00196.x

M. Yang, M. L. Scattoni, V. Zhodzishsky, T. Chen, H. Caldwell, W. S. Young, H. G. McFarlane, J. N. Crawley, Social Approach Behaviors are Similar on Conventional Versus Reverse Lighting Cycles, and in Replications Across Cohorts, in BTBR T+ tf/J, C57BL/6J, and Vasopressin Receptor 1B Mutant Mice, Frontiers in Behavioral Neuroscience 1 (2007). pp. 1. doi:10.3389/neuro.08.001.2007

M. Yang, V. Zhodzishsky, and J. N. Crawley, Social Deficits in BTBR T+tf/J Mice are Unchanged by Cross-Fostering with C57BL/6J Mothers, International Journal of Developmental Neuroscience 25(8) (2007), pp. 515–521. doi:10.1016/j.ijdevneu.2007.09.008