Document Type


Date of Award

Winter 12-1-2021

Degree Name

Master of Science (MS)



First Advisor

Summers, Cliff H.


Depressive mood disorders are a leading cause of disability worldwide and pharmacological treatments for these disorders are inadequate, requiring new compounds with greater efficacy be investigated. The etiology of depression is heterogeneous; however, it is well established that stress exposure, and the proinflammatory effects of stress have a major role. Psychedelic compounds have rapid and long-lasting anxiolytic and antidepressive effects in humans and animal models of stress induced affective behavior. However, it is not completely understood how these compounds produce such rapid effects. We investigated whether the psychedelic compound (R)-2,5-dimethoxy-4-iodoamphetamine [(R)-DOI], a selective 5-HT2A partial agonist with potent anti-inflammatory properties, influences stress-related behavior in mice exposed to repeated social aggression, and if these behavioral changes are related to the anti-inflammatory properties of this compound. Animals were subjected to the Stress Alternatives Model (SAM), an escapable social stress paradigm where animals develop either passive coping strategies like remaining in the SAM arena (Stay) with a social aggressor, or active stress coping strategies that involve utilizing the escape holes (Escape) to avoid aggression. Mice expressing these behavioral phenotypes display behaviors like those in other social aggression models that separate animals into stress-susceptible or stress-resilient groups, which have been shown to have distinct inflammatory responses to social stress. These results show that Stay and Escape animals have heightened blood plasma concentrations of the inflammatory cytokine tumor necrosis factor-α (TNF-α) compared to unstressed control mice. Additionally, these results suggest that a single administration of (R)-DOI to Stay animals in low doses, can increase active stress coping strategies such as increasing attention to the escape route, promoting escape behavior, and reducing conflict freezing in the SAM. In Escape animals, the middle-dose of (R)-DOI shifted behavior in a way that suggests it may have had acute anxiogenic effects in certain behavioral measures.

Subject Categories

Biology | Neurosciences


(R)-DOI; Inflammation; Stress

Number of Pages



University of South Dakota



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