Molecular Horizons PhD Exit Seminar - Ilijana Babic

Antipsychotic drugs olanzapine and clozapine are used to treat schizophrenia; however, they are limited in their ability to treat cognitive symptoms and often cause detrimental side effects including obesity and diabetes. Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist and antidiabetic drug with anti-obesity and neuroprotective properties. This thesis employed a female rat model of antipsychotic drug-induced metabolic dysfunction developed in our laboratory to investigate whether chronic liraglutide co-treatment with olanzapine and clozapine could prevent metabolic side effects and at the same time, improve cognition. Further, the effects of liraglutide co-treatment on central and peripheral markers of metabolism and cognitive function were investigated. This thesis shows for the first time that liraglutide co-treatment can prevent aspects of metabolic and cognitive dysfunction induced by antipsychotic drugs and can prevent abnormalities in the expression of key neurochemicals in brain regions central to cognition. These findings highlight the possible connection between metabolic and cognitive health and support further investigation into GLP-1 receptor agonists for the treatment of serious mental illness.