Date of Completion
Dr. John Salamone
Physiology and Neurobiology
Depression is a debilitating disorder that is accompanied by a variety of motivational symptoms, many of which are only minimally treated by common antidepressants. Not much is known about the underlying brain activity that is associated with these symptoms. This study utilized several different techniques to investigate the neural processes related to an animal model of depression and the motivational symptoms that accompany the disorder. Progressive ratio (PROG) tasks have been used to assess animals’ willingness to exert high levels of work to obtain highly valued reinforcers. In this experiment, a novel version of the PROG schedule was developed to cause rats to exhibit a “breakpoint” at which the ratio requirement is too difficult and they stop responding. This experiment involved administration of tetrabenazine in rats to assess effort-related performance changes on the PROG task. It was determined that tetrabenazine produced effort-related impairments that mimic the motivational deficits associated with depression in humans. The breakpoint seen under baseline conditions was used as a comparison under various pharmacological conditions, which will also be useful for future electroencephalography studies. Recordings of animals’ electroencephalography activity were measured after the rats were injected with tetrabenazine or vehicle control and were compared across conditions to determine if tetrabenazine produced changes in activity. A reduction in power spectral density of brain waves at higher frequencies in both frontal and parietal cortices after tetrabenazine injection was observed. These physiological and behavioral data may have implications for humans with depression, while laying the groundwork for new treatment options.
Canfield, Danielle E., "Effects of Tetrabenazine on Work Output in Rats Responding on a Novel Progressive Ratio Task: Behavioral, Pharmacological, and Electrophysiological Studies" (2020). Honors Scholar Theses. 753.