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Interclass Gpcr Heteromerization Affects Localization And Trafficking, Rudy Toneatti

Theses and Dissertations

Class A serotonin (5-hydroxytryptamine) 2A (5-HT_2AR) and class C metabotropic glutamate 2 receptors (mGluR2) are seven transmembrane receptors (7TMRs or G protein-coupled receptors – GPCRs) involved in multiple neuropsychiatric disorders including schizophrenia. Previous findings from our laboratory reported that 5-HT_2AR and mGluR2 are dysregulated in the prefrontal cortex of patients suffering from this psychiatric condition, although 5-HT_2AR’s expression was recovered in antipsychotic-medicated patients. Genome-wide association studies on schizophrenia reported that endosomal trafficking that regulates cell surface abundance of another 7TMR implicated in this disease (dopamine D2 receptor) can be altered. Ligand-activated receptors, including the …

Glucocorticoid Receptor Dysregulation Underlies 5-Ht2a Receptor-Dependent Synaptic And Behavioral Deficits In A Mouse Neurodevelopmental Disorder Model, Justin M. Saunders

Theses and Dissertations

Schizophrenia is a severe neuropsychiatric disorder that presents with diverse symptoms, some of which remain resistant to treatment. Increased risk of neurodevelopmental disorders such as schizophrenia has been observed following gestational infection in humans, leading to development of maternal immune activation (MIA) animal models. Increased density of the serotonin 5-HT2AR receptor (5-HT2AR), the primary target of hallucinogenic drugs and a key target of atypical antipsychotics, has been observed in postmortem antipsychotic-free prefrontal cortex samples from schizophrenia subjects, a change reflected in frontal cortex of adult MIA offspring. To model MIA, we administered 20 mg/kg i.p. of the viral mimetic poly-(I:C) …

Pharmacophoric Evaluation Of 5-Ht2a And 5-Ht2b Serotonin Recpeptors, Prithvi Hemanth

Theses and Dissertations

Serotonin (5-HT) receptors represent a class of receptors involved in a variety of physiological processes including regulation of mood, perception, cognition, appetite, and heart function, and thus serve as drug targets of several drugs such as antipsychotic agents, hallucinogenic drugs, and appetite suppressant drugs. Due to the structural similarity of certain 5-HT receptor subtypes, particularly 5-HT₂ receptors (5-HT_2A, 5-HT_2B receptors) determination and refinement of pharmacophore models of these receptor subtypes can greatly improve the therapeutic efficacy of drugs that target them.

The goals of this study were to define and/or refine existing pharmacophore models for 5-HT …