Date of Award


Degree Type


Degree Name

Master of Science


Anatomy and Cell Biology


Dr. Raj Rajakumar, PhD

Second Advisor

Dr. Kem Rogers, PhD


Atypical antipsychotic drugs are associated with increased weight gain, which often leads to patient non-compliance and decreased quality of life among individuals with schizophrenia. It is proposed that atypical antipsychotics facilitate metabolic disturbances by disrupting hypothalamic control of feeding and energy homeostasis. The first aim of this thesis focused on the development of a reliable animal model of antipsychotic-induced weight gain. Female Sprague Dawley rats received daily oral administrations of olanzapine for 14 days. After sub-chronic treatment, these animals were sacrificed to analyze the expression of specific hypothalamic peptides involved in leptin signaling pathways, specifically phosphorylated signal transducer and activator of transcription (pSTAT3), pro­ opiomelanocortin (POMC) and Agouti-related peptide (AgRP). Immunohistochemistry was used to localize and quantify the number of pSTAT3- immunoreactive neurons in the ventromedial nucleus (VMH) and arcuate nucleus (ARC) of the hypothalamus. POMC and AgRP immunoreactivity was quantified in the ARC. Results show that sub-chronic administration of olanzapine in female rats is associated with decreased pSTAT3 in the VMH and reduced POMC in the ARC. These findings implicate a possible mechanism of antipsychotic-induced weight gain by dampening anorexigenic signals via reduced pSTAT3 and POMC expression.



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