Autism spectrum disorder (ASD) and schizophrenia are neuropsychiatric diseases with origins in development, genetics and the environment. Understanding how environmental influences converge with genetic predispositions during specific developmental windows to create a sensitive period is the key to discovering the etiology of and potential therapeutic treatments for these complex disorders. This proposal explores how a specific environmental influence, inflammation and the medications that treat it, can selectively alter brain development and create vulnerability where none existed. Using the laboratory rat, this research will investigate the novel concept that inflammation during a restricted sensitive period leads to excess prostaglandin E2 (PGE2), a proinflammatory molecule that stimulates aromatase activity and estradiol synthesis locally within the cerebellum. Excessive estradiol stunts the outgrowth of Purkinje neuron dendrites by up-regulating GABA (gamma amino-butyric acid) synthesis. Conversely, exposure to anti-inflammatory medications such as NSAIDs (non-steroidal anti-inflammatory drugs) or acetominophen has the opposite effect, causing exuberant dendritic sprouting. The data generated by these experiments will highlight a previously unexpected source of risk for developmental neuropsychiatric disease, prostaglandins elevated during inflammation and/or the frequently used medications designed to block inflammation. Understanding how inflammation and the medications taken to treat it impact the developing cerebellum will provide important mechanistic insight into the origins of these disorders of mental health.