765. Phosphorylation Mapping Reveals New Brain Networks Linked by Antipsychotic Drugs

Abstract

Abstract Background While the target molecules for neuropsychiatric drugs have been identified, their specific mechanisms of action within brain regions and cells are still unknown. To enhance mental health treatments, it is crucial to conduct a comprehensive analysis of the effects of current therapeutic agents on different portions of the individual’s brain. This will facilitate the development of better treatment strategies, minimize side effects, and ultimately improve mental health outcomes. Aims & Objectives Schizophrenia is broadly divided into positive symptoms, which include hallucinations and delusions; negative symptoms, which include a decline in emotions and motivation; and cognitive impairment. While drug therapy for schizophrenia is effective in alleviating positive symptoms, it is limited in its effectiveness against negative symptoms, which is a challenge in treatment strategy. This problem stems from the opacity of the brain network on which antipsychotic drugs act. To address these challenges, we require an innovative approach that comprehensively elucidates the molecular basis of the entire brain. This study aims to elucidate the effects of antipsychotic drugs on the brain and the signaling pathways that regulate neuronal activity. Method We developed an imaging technique that uses specific anti-phosphorylation antibodies against protein kinases and their substrates to evaluate the activity of signaling pathways throughout the brain. We investigated the effects of various antipsychotic drugs on signaling pathways in the brain. We conducted a detailed study of the entire brain in mice that received antipsychotic drugs and in those that did not, to find out which pathways and brain areas were active in the treated mice compared to the control mice. Results It became clear that first- and second-generation antipsychotic drugs activate different signaling pathways in the basal ganglia. Furthermore, it was found that the second-generation antipsychotic clozapine activates the ERK pathway in different brain regions compared to other drugs. Clozapine, often used for schizophrenia that doesn't respond to other treatments, will be studied more to understand how it affects different parts of the brain and changes the behavior of test animals to improve symptoms of schizophrenia. Discussion & Conclusions The results of this study make it possible to distinguish the effects of different antipsychotic drugs on the brain network. The phospho-ERK mapping analysis results from the brains of mice administered various antipsychotic drugs will demonstrate the affected neural circuits, helping to identify how these drugs work to treat schizophrenia under our experimental conditions.