Award Date

5-1-2025

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Interdisciplinary Programs

First Committee Member

Rochelle Hines

Second Committee Member

Dustin Hines

Third Committee Member

Kelly Tseng

Fourth Committee Member

Allyson Hindle

Number of Pages

189

Abstract

Psychoactive drugs are a class of substances which alter cognition, mood, and conscious states. While the effects of psychoactives are readily identifiable in humans, their characterization in rodents remains challenging due to limited and contradictory behavioral outcomes. In the present studies, we perform systemic studies utilizing an integrative assessment of rodent behavior and electroencephalography (EEG) to reliably identify distinct correlates of psychoactive drug activity. First, we screen a novel library of carvone-derived cannabidiol (CBD) congeners and observe compound-specific changes to EEG frequency bands. We then test the efficacy of a lead compound in attenuating seizure and observe a reduction in seizure induced mortality and normalizing effects on aberrant neuronal morphology. Second, we find that mice treated with a potent and specific serotonin receptor type 2A (5-HT2AR) agonist display behavioral arrest and temporally coupled EEG waveforms (P1; P2) in addition to the canonical readout of psychedelic activity in rodents (head-twitch response; HTR). We manipulate these hallmarks by pretreating mice with nicotine and observe enhancement of behavioral arrest and P1 with attenuation of the HTR and P2. Third, we screen the effects of tryptamine, phenethylamine, and ergoline psychedelics. We observe drug and dose specific ethological behavior patterns, changes in frequency and power of P1 and P2, and altered neuronal spine morphology. These studies demonstrate that psychoactives, even within the same drug class, have distinct behavioral and EEG signatures. Further, these findings inform preclinical screening of psychoactives with increased validity to advance the identification and development of novel compounds for personalized medicine.

Controlled Subject

Psychotropic drugs; Psychology

Disciplines

Medical Neurobiology | Neuroscience and Neurobiology | Neurosciences

File Format

pdf

File Size

4700 KB

Degree Grantor

University of Nevada, Las Vegas

Language

English

Rights

IN COPYRIGHT. For more information about this rights statement, please visit http://rightsstatements.org/vocab/InC/1.0/

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Available for download on Monday, May 15, 2028


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