Modeling Astrocyte Influence on Risperidone Response in Neuropsychiatric Treatment - Using COPASI

Bipolar disorder and schizophrenia are prevalent neuropsychiatric disorders.Risperidone is an antipsychotic drug that has variability among patient responses to it.Astrocytes play a critical role in regulating neurotransmitter levels, particularly glutamate.Glutamate is the primary excitatory neurotransmitter; elevated glutamate concentrations in the synapse can lead to excitotoxicity, potentially influencing the efficacy of risperidone.This research aims to find how astrocytic glutamate uptake influences risperidone's efficacy.A computational simulation was developed using COPASI, a biochemical pathway modeling tool, to explore the dynamics of dopamine and risperidone binding to the D2 under a high glutamate concentration of 5 μmol/L.Two trials were conducted: a normal astrocyte model with active glutamate uptake, and a defective astrocyte model, where glutamate uptake was absent (V max set to 0).Other values were held constant.The results showed that despite simulating excitotoxic conditions with high glutamate levels in both models, there was no significant change in risperidone's binding efficacy to the D2 receptor compared to the normal astrocyte model.These observations suggest that, under the utilized experimental conditions, glutamate uptake by astrocytes does not directly influence the rate of risperidone binding to the D2 receptor.This suggests that there may be other mechanisms influencing risperidone response.