Chronic Treatment with Risperidone Modulates Molecular Signaling in the Prefrontal Cortex and Hippocampus

Abstract

Risperidone is a commonly prescribed antipsychotic drug that is used to treat schizophrenia, bipolar disorder and relieve irritability in autistic children. Antipsychotics are believed to work by modulating neurotransmission events such as the synaptic neurotransmitter-to-receptor interactions towards dopamine receptors to improve mood and behavior. Chronic treatment with risperidone may negatively affect learning and memory through mechanisms mediated by epigenetic changes, such as histone post-translational modifications. We completed behavioral and molecular studies and found that the results of the behavioral studies of risperidone treated show that the rats treated with risperidone may be cognitively impaired. Our molecular work showed a trend of decreased total histone H3 protein throughout the hippocampus and the prefrontal cortex and increased acetylation in both the hippocampus and prefrontal cortex after chronic exposure to Risperidone for 180 days via drinking water, potentially indicative of a compensatory mechanism to increase protein expression, attempting to subsist with loss of total protein. If the prefrontal cortex and the hippocampus are not working properly due to a disruption in cellular homeostasis, then there may be an issue with long and short term memory, eventually leading to impaired cognitive processes. Further studies will need to be done such as probing the hippocampus and pre-frontal cortex for additional post-translational modifications to lysine residues such as methylation and expression of proteins associated with the molecular mechanisms that underlie memory function in other parts of the prefrontal cortex and hippocampus to develop a full story of the chronic effects of risperidone.