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The wide variation and overlap in symptoms across disorders increases the difficulty of research and treatment development. The NIMH Research Domain of Criteria initiative aims to improve our understanding of the molecular and behavioral consequences of aspect neurodevelopmental mechanisms across disorders, enabling beleaguered treatment development. The transcription factor Specificity Protein 4 SP4 is important designed for neurodevelopment and is genetically associated along with both schizophrenia and bipolar disorder. Abridged Sp4 expression in mice hypomorphic reproduces several characteristics of psychiatric disorders. We further tested the utility of Sp4 hypomorphic mice as a model being relevant to psychiatric disorders by assessing cognitive control plus effort and decision-making aspects of approach motivation using cross-species-relevant tests. Sp4 hypomorphic mice exhibited impaired attention as measured by the 5-Choice Continuous Performance Test, an effect so as to was attenuated by glycine type-1 carrier GlyT-1 inhibition. Hypomorphic mice also exhibited reduced motivation to work for a reward and impaired probabilistic learning. These deficits may stem from affected blocking reward, analogous to anhedonia in patients with schizophrenia and other psychiatric disorders.

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