Date of Completion

Spring 5-12-2023

Thesis Advisor(s)

John Salamone, Alev Ecevitoglu

Honors Major

Individualized Major

Disciplines

Behavioral Neurobiology | Biological Psychology | Cognitive Neuroscience | Experimental Analysis of Behavior

Abstract

Major depression is a devastating disorder that consists of multiple symptoms such as low mood and motivational dysfunction. It has been shown that motivational dysfunction can be studied in animal models by using effort-based choice paradigms, which vary in their response requirements. It has been reported that dopamine depletion in the nucleus accumbens decreases ratio-scheduled lever-pressing in a manner related to the size of the ratio requirement. One dopamine depleting agent is tetrabenazine (TBZ), which has been shown to decrease lever-pressing and induce low-effort bias. The current study aims to investigate behavioral and electrophysiological changes that occur with animals performing on operant schedules with different work requirements and determine how tetrabenazine administration affects behavior and physiology. Forty animals were trained on various operant schedules for 5-6 weeks with 8 animals on FR1, 8 animals on FR5, 8 on FR10, 8 on FR20, and 8 on FR40. Upon training completion, rats were treated with TBZ and a vehicle (VEH) in two consecutive weeks, and their lever-pressing numbers were recorded. The results present that TBZ administration decreases the number of lever presses in each work requirement (t-tests, p<0.05). Next, the rats trained on FR5, FR10, and FR20 underwent stereotaxic surgeries, in which electrodes were bilaterally placed into the nucleus accumbens and additional structures, like the parietal cortex, to record local field potentials. Following recovery, rats were administered TBZ or a VEH while both lever-pressing response and local field potentials were recorded. Initial analyses of local field potentials suggests that there is synchronization between peak lever-pressing and the following peak of theta waveforms in the nucleus accumbens with some aspects comparable between different fixed-ratio scheduled animals. This study increases our understanding of motivational dysfunction in terms of behavior as well as electrophysiology.

COinS