Date of Completion


Thesis Type

College of Arts and Science Honors


Psychological Sciences

First Advisor

Sayamwong Hammack


Depression, PACAP, Chronic Stress, Medial Habenula


Major Depressive Disorder (MDD) is a mood disorder with a prevalence of nearly 300 million people worldwide, and incidence has been increasing annually. While the mechanisms causing depression are not fully understood, pituitary adenylate cyclase-activating peptide (PACAP) and its receptor PAC1 have been implicated in the pathogenesis of depression. The Medial Habenula (MHb) is a region of the brain with an abundance of PACAP projections and receptors that is thought to be a major brain area involved in the mechanisms underlying depression. The current project uses a chronic unpredictable mild stress paradigm to induce depressive-like behaviors in a rat model and tests the effect of a novel-small molecule PAC1 antagonist on these depressive-like behaviors through a sucrose preference test. The novel-small molecule antagonist was infused directly into the MHb in order to further investigate the role of the MHb in depression. While data from the current experiment alone did not show a significant effect of the antagonist on depressive-like behaviors, when this data was combined with previous data from our lab the novel small-molecule antagonist did have a significant effect on depressive like behavior in stressed rats compared to stressed rats that received a vehicle infusion into the MHb. This project adds to our knowledge on the MHb’s role in depression, the role of PACAP in depression, and suggests that the small-molecule PACAP antagonist JF-214 is a possible treatment for MDD.

Available for download on Sunday, May 10, 2026