Publication Date

Spring 2014

Degree Level

B.S.

Program

Honors

First Advisor

Contreras-Shannon, Veronica

Second Advisor

Uhlig, Paul

Document Type

Thesis

Medium

Manuscript

Abstract

Haloperidol is a first generation antipsychotic that is used to treat symptoms of psychosis in patients affected by schizophrenia. This class of antipsychotics is associated with neurological side effects. On the other hand, atypical antipsychotics, such as Clozapine, are associated with metabolic side effects. Ln order to better understand the metabolic basis for the different side effects, we compared the two classes of antipsychotics. Yeast was grown in the presence of Haloperidol on both fermentable and non fermentable carbon sources at concentrations of 0 uM, 1 uM, 5 uM, and 10 uM. The resultant cell viability and the reactive oxygen species (ROS) production were studied and compared to yeast studies with Clozapine. The hypothesis was that increasing concentrations of Haloperidol would decrease cell viability and increase the production of ROS in a different way than was observed for Clozapine owing to the fact that these antipsychotics have completely different mechanisms. The antioxidant, N acetylcysteine, was also tested to see if it had a protective effect on the cell and recovered cell viability while decreasing ROS, as expected. In glycerol and glucose, there was a dose-dependent decrease in cell viability and increase in ROS with increasing concentration of Haloperidol. Lactate and ethanol had results that were not dose-dependent. The results from the experiments with Clozapine and Haloperidol suggest a difference in the mechanisms of the antipsychotics.

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