This project represents a consortium of basic researchers with expertise in rodent models of autism spectrum disorders who seek to discover effective treatments for the core symptoms of autism. Mice and rats with genetic mutations associated with autism display abnormal social behaviors, reduced vocalizations, stereotyped circling, repetitive self-grooming, seizures, anxiety-like behaviors, and cognitive deficits. These symptoms in mice and rats will be used as preclinical assays to test potential drug treatments. Pharmacological interventions will be assessed for their ability to restore normal sociability and communication skills, to reduce repetitive behaviors, to lessen seizures and anxiety-like behaviors, to correct hypo- and hyper-responsivity to sensory stimuli, and to improve cognitive disabilities. The choice of pharmacological compounds will be based on knowledge about the genetic mutations associated with autism which act to impair synaptic connections between neurons in the brain. Compounds that reproducibly reduce symptoms in both mouse and rat models of autism will point the way to clinical trials for medications to improve the diagnostic and associated symptoms of autism.