There is a growing consensus in the scientific community that believes that a treatment for Angelman syndrome (AS) is not just possible, but very probable. However, the lack of known therapeutic targets at the cellular level that underlies the mechanisms of AS has hampered the development of therapeutic strategies. Couple that with the laborious and timely task of obtaining FDA approval once a therapeutic strategy is found, it quickly becomes evident that a treatment for AS is years or maybe even decades away. With these roadblocks in mind, this proposal tries to circumvent both of these deficiencies in regard to successfully and responsibly developing a therapeutic strategy for the treatment of AS. In this regard, this proposal does not focus, necessarily, on understanding mechanisms of AS but rather treating AS. Two main concepts were taken into consideration when I developed this proposal: shortening the time to elucidate the underlying mechanisms of AS and shortening the amount of time to have a therapeutic strategy FDA approved. This was accomplished in two ways; 1) Use pharmacological agents that are known have correlates to counter the molecular or cognitive deficiencies involved with AS. 2) Use pharmacological agents that are already FDA approved for use in humans and have an established treatment regimen. The use of these two strategies will significantly reduce the amount of time from experimental testing, to preclinical evaluation to a working and publicly available treatment for AS. To test the validity of these compounds, the AS mouse model will be used and four compounds tested and treated AS mice compared to wild-type mice at the levels of 1) Degree of cognitive enhancement 2) Rectification a biological and genetic abnormalities 3) Increases in neuronal connectivity and neuronal efficiency. It is my hope that one of these compounds will have a positive effect on one or more of these aspects that underlie AS. Furthermore, any and all positive results will prompt a full preclinical evaluation of the compound(s) and could potentially lead to the development of an effective AS therapeutic strategy.