EFFECTS OF SIGMA-1 RECEPTOR AGONISTS ON COMPULSIVE BEHAVIOR AND NEUROPLASTICITY

Author

Shelby F. RoesnerFollow

Date of Award

6-2025

Degree Type

Thesis

Degree Name

Master of Science

Department

Psychological Science

Program

Psychological Science (MS)

First Advisor/Chairperson

Adam Prus

Abstract

Compulsivity is a feature of many psychiatric disorders, resulting in distressing and challenging to treat symptoms. Compulsivity is a key feature of obsessive compulsive disorder, which can hinder a person's life and ability to work. Selective serotonin reuptake inhibitors are the current treatments for these disorders, which take 8-12 weeks to take effect and leave many patients without adequate treatment gains. Delayed treatment effects may be due to neuronal proliferation involving mammalian target of rapamycin (mTOR). Preclinical studies suggest that sigma-1 receptor agonists produce antidepressant-like drug effects and affect the mTOR pathway. Other mechanisms include serotonin neurotransmission and N-methyl-D-aspartate (NMDA) receptors. This study evaluated drugs acting as sigma-1 agonists, NMDA receptor antagonists, and serotonin reuptake inhibitors in preclinical animal behavior models for assessing treatments for obsessive compulsive disorder, the marble burying test, and depression, the novelty suppressed feeding test. Further, a Western blot assessment was conducted with dextromethorphan, which is a compound that exhibits all three pharmacological actions of interest for this study. The NMDA receptor antagonist S-ketamine, the sigma 1 receptor agonist SA4503, dextromethorphan (after subcutaneous, but not intraperitoneal, administration), the sigma 1 agonist and serotonin reuptake inhibitor fluvoxamine, and the serotonin reuptake inhibitor paroxetine significantly reduced marbles buried, but did not affect response latency in the novelty suppressed feeding test. Only fluvoxamine exhibited reduced marbles buried up to 72 hrs post treatment. Dextromethorphan did not affect levels of phosphorylated mTOR. Overall, these findings lend support for novel pharmacological actions to treat obsessive compulsive disorder. Methodological considerations are discussed.

Recommended Citation

Roesner, Shelby F., "EFFECTS OF SIGMA-1 RECEPTOR AGONISTS ON COMPULSIVE BEHAVIOR AND NEUROPLASTICITY" (2025). All NMU Master's Theses. 894.
https://commons.nmu.edu/theses/894

Access Type

Open Access

Justification for Restricting Access

My thesis advisor and I would like to try and publish the results from my thesis in a journal article.