The Effect of Betahistine on Modulating Olanzapine-Induced Metabolic changes: Role of Oxidative Stress in a Rat Model of Schizophrenia

Abstract

Second-generation antipsychotics have been substantially used in treatment of psychiatric disorders during the past decade, among them, olanzapine was shown to have well-known efficacy to treat schizophrenia with greater tolerability, while the metabolic side effects induced by its use have raised the need to exploring further mechanisms to ameliorate these side effects. Accumulated evidence has shown a potential relationship between antipsychotic drug affinity for specific receptors and metabolic side effects. In particular, H1 receptor antagonism has been identified as the main contributor to olanzapine -induced body weight gain/obesity side effects. Recently, co-treatment with betahistine (a histamine H1 receptor agonist H3 receptor antagonist) has been shown to improve OLA-induced weight gain. It is also hypothesized that oxidative stress may play a role in SGA induced side effects, in addition it has been implicated in the pathophysiology of schizophrenia Since betahistine has a very high safety profile it has a huge potential for chronic management of antipsychotic-induced weight gain and obesity in schizophrenia Therefore, inspection further to the betahistine role would be helpful when using the isolation rearing model, a valid, realistic simulation of schizophrenia in animals.