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 neurotransmitter-synaptic membrane receptor interactions towards dopamine receptors to improve mood and behavior. Chronic treatment with Risperidone, while it does have many positive effects on the symptoms of psychotic ailments such as irritability, may negatively affect learning and memory through epigenetic changes. Epigenetic changes can include histone modifications, which are indirectly associated with chronic use of antipsychotics. We completed both a behavioral study and a molecular study and found that chronic use of Risperidone does materialize a basis for cognitive impairments. For example, our passive avoidance test showed that the rats treated with Risperidone had cognitive impairments. Coupled with our molecular work, we found a trend of decreased acetylation at 90 days and then increased acetylation at 180 days and decreased total protein throughout, indicating that the brains of the rats are trying to increase protein expression by increasing acetylation, trying to cope with the loss of total protein. Further studies will need to be done such as probing for methylation and looking at protein expression in other parts of the pre-frontal cortex and hippocampus to develop a full story of the chronic effects of Risperidone on the brain.