University Honors, Honors in Psychology
Date of Award
Russell W. Brown
Thesis Professor Department
Matthew Palmatier, Gregory Ordway
Research has revealed that current antidepressant treatment is less than adequate at alleviating behavioral endophenotypes associated with major depressive disorder (MDD) and there is a need for appropriate animal models to validate novel antidepressant pharmacological targets. In the present study, we wished to establish an ethologically relevant social defeat stress model in combination with a chronic unpredictable stress model, to more accurately mimic severe stress that is common in MDD. Before each day of the introduction of the stressor, animals were given saline or a 40 mg/kg dose of 3-aminobenzamide (3-AB), a poly ADP-ribose (PARP) inhibitor. PARP is a DNA repair enzyme that is increased in activity in response to DNA oxidation, which is elevated in the prefrontal cortical white matter in MDD post-mortem donors. One stressed group was given the common antidepressant fluoxetine (10mg/kg) to serve as a positive control. Results of this study demonstrated that 3-AB alleviated decreases in sucrose preference, a natural reward, along with avoidance on a social interaction test given at the end of social defeat. Preliminary telemetry readings indicated 3-AB was able to significantly decrease heart rate and blood pressure in response to SDS as compared to saline treated rats. Therefore, it appears that PARP inhibition alleviated behavioral endophenotypes associated with stress and represents a new pharmacological treatment for MDD in humans.
East Tennessee State University
Honors Thesis - Withheld
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De Preter, Caitlynn, "Poly ADP-Ribose Protein (PARP) Inhibition Alleviates Behavioral Endophenotypes Due to Stress in a Rodent Double-Hit Model of Major Depressive Disorder (MDD)" (2017). Undergraduate Honors Theses. Paper 412. https://dc.etsu.edu/honors/412
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