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

<p>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.</p>

Name thesis:degree_name

Master of Science

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Psychological Science

Year dc:date.available

2025

Author dc:creator

• Roesner, Shelby F

Contributors dc:contributor

• Adam Prus

• S Ketamine
• Fluvoxamine
• MBT
• Sigma-1 Receptor
• NMDA Receptor
• Sustained effects
• NSF
• Paroxetine
• SA4503
• Dextromethorphan
• Animal Studies
• Behavior and Behavior Mechanisms
• Other Pharmacy and Pharmaceutical Sciences
• Psychological Phenomena and Processes

Repository record dc:identifier

https://commons.nmu.edu/theses/894

OAI identifier oai:identifier

oai:commons.nmu.edu:theses-1960