Date of Award

8-2026

Document Type

Thesis

Degree Name

Master of Arts in Psychological Science

Department

Psychology

First Reader/Committee Chair

Amodeo, Dionisio

Abstract

Selective Serotonin Reuptake Inhibitors (SSRI) are the most common form of medication prescribed to people with anxiety disorders. One of the most common side effects is weight gain. This weight gain often leads to the suspension of treatment. This has led to studies focusing on specific serotonin (5-HT) receptor targets for modulating depression and anxiety. Studies examining 5-HT6 antagonist treatment have shown that they reduce body weight as well as produce brain specific changes. Less is known regarding 5-HT6 receptor agonists, although previous literature has shown that exposure to high doses produces weight loss but not at lower doses, while anxiolytic effects are mixed. This current study investigated the impact of repeated 5-HT6 receptor activation with EMD386088 on measures of weight and anxiety. Mice received daily injections of EMD386088 at either 0, 1, or 5 mg/kg for 14 days. The mice had their weights recorded daily. On days 1, 14 and 21 mice were tested on the elevated plus maze. It is predicted that mice given the higher dose will show reduced body weight and will exhibit anxiolytic effects, whereas mice given the lower dose are expected to show no change in weight but still display an anxiolytic effect. As expected, C57BL/6J and BTBR male mice weighed more than female mice across the 14 days. There was a significant main effect of day, as body weight increased over the two weeks of treatment. In addition, there was a significant sex‑by‑day interaction: male BTBR mice gained the most weight across the study period. For open‑arm time, female C57BL/6J mice treated with 5.0 EMD386088 spent less time in the open arm compared saline or 1.0 EMD386088 treated mice. On Day 14 the BTBR mice treated with saline spent more time in the open arm than mice treated with the 1.0 EMD 386088, thus two weeks of treatment lead to an anxiogenic effect. On Day 21, female BTBR mice showed the same pattern, whereas male BTBR mice treated with 5.0 EMD 386088 spent more time in the open arm than male BTBR mice in the 1.0 EMD 386088 condition. There was a significant main effect of time: on Days 14 and 21, mice spent more time in the open arm compared to Day 1, demonstrating that repeated EMD386088 treatment also led to anxiolytic effects. Lastly, there was a significant interaction such that open‑arm time increased across the study for the saline and 5.0 EMD 386088 conditions but not for the 1.0 EMD 386088 condition. These findings suggest that repeated activation of the 5‑HT6 receptor using the agonist EMD 386088 had little to no impact on body weight aside from expected sex‑ or age‑related differences in both mouse strains. Open‑arm time increased for the BTBR mice but only at the highest dose. Overall, activation of the 5‑HT6 receptor may have played a role in weight gain while also producing anxiolytic effects, but these effects were observed only in the BTBR mice.

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