Date of Completion

Spring 5-1-2023

Thesis Advisor(s)

John Salamone

Honors Major

Biological Sciences

Abstract

Pergolide is an ergot derivative dopamine agonist which acts on the dopamine D2 and D3, alpha2- and alpha1-adrenergic, and 5-hydroxytryptamine receptors. It was previously used as a treatment for the symptoms of Parkinson’s disease, but was taken off of the market as a result of causing increased risk of heart disease. As a dopamine agonist, pergolide stimulates D2 receptors, which are associated with improvement of symptoms of movement disorders. This link exists because the highest concentration of D2 receptors in the brain is in the basal ganglia, which is involved in motor control. Given the connection between pergolide, dopamine, and motor function, this paper analyzes the effects of pergolide on motivation related to depression. Individuals who have been diagnosed with depression show decreased locomotion, which is correlated with the severity of the depression. The symptoms associated with depression of lethargy and low motivation can be modeled in rats using the vesicular monoamine transporter inhibitor tetrabenazine (TBZ), which depletes dopamine. It has been shown that dopamine transport blockers such as bupropion and GBR12909 can reverse the effects of TBZ in rats, but this study will investigate the effects of a dopamine receptor agonist on motivation. Using an FR-5 fixed- ratio/chow feeding choice task, laboratory rats are given the option of choosing to either press the lever and receive a preferred high carbohydrate pellet or approach and consume the less preferred lab chow provided concurrently in the operant conditioning box. TBZ reduces selection of lever pressing, and it was hypothesized that treatment with pergolide would reverse the effects of TBZ and increase lever pressing in the effort-related choice task.

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