Behavioral and molecular effects of the antipsychotic drug blonanserin in the chronic mild stress model

Abstract

Psychiatric disorders represent a critical challenge to our society, given their high global prevalence, complex symptomatology, elusive etiology and the variable effectiveness of pharmacological therapies. Recently, there has been a shift in investigating and redefining these diseases by integrating behavioral observations and multilevel neurobiological measures. Accordingly, endophenotype-oriented studies are needed to develop new therapeutic strategies, with the idea of targeting shared symptoms instead of one defined disease. With these premises, here we investigated the therapeutic properties of chronic treatment with the second-generation antipsychotic blonanserin in counteracting the alterations caused by 7 weeks of Chronic Mild Stress (CMS) in the rat. CMS is a well-established preclinical model able to induce depressive and anxiety-like alterations, which are shared by different psychiatric disorders. Our results demonstrated that the antipsychotic treatment normalizes the CMS-induced emotionality deficits, an effect that may be due to its ability in modulating, within the prefrontal cortex, redox mechanisms, a molecular dysfunction associated with several psychiatric disorders. These evidences provide new insights into the therapeutic properties and potential use of blonanserin as well as in its mechanisms of action and provide further support for the role of oxidative stress in the pathophysiology of psychiatric disorders.