Month/Year of Graduation

5-2023

Degree Name

Bachelor of Science in Molecular and Biomedical Biology (BTCHBS)

Department

Neuroscience

First Advisor

Erik Garcia, PhD

Abstract

The prevalence of substance use disorders (SUDs) continues to rise while the number of medications to combat this deadly disorder remains stagnant. Entirely new thinking about what exemplifies a possible therapeutic is needed. Hallucinogens are continually being studied more as possible treatments for many psychological conditions, including SUDs. Classic hallucinogens engage many serotonin and monoamine systems, but the hallucinogenic effects are driven by serotonin 5-HT2A receptor (5-HT2AR) activation. Forced social isolation induces chronic stress, increases 5-HT2AR expression in the cortex and have been suggested to play a role in the comorbidity between stress, maladaptive coping, and SUDs. In this experiment, we manipulated a critical developmental period to determine the extent to which environmental variables affect 5-HT2AR activity and behavior. Male and female rats were reared in a socially enriched or isolated condition for 30 days. After 30 days, all rats were treated with the 5-HT2AR agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) over 5 weeks. Head twitch responses – a behavioral proxy for hallucinogenic activity – were scored. Results indicated that sex and environment change the head twitch response, such that females and enrichment-reared rats were most sensitive to DOI. The potency shift in females and enriched rats suggest that 5-HT2AR may be upregulated in these groups. These findings suggest that environmental enrichment could be an important mediator in successfully treating SUDs, and that social environment and sex are factors to consider when using hallucinogens as therapeutics.

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