In the McMurray Lab, we study the behavioral and molecular effects of hallucinogenic drugs on serotonergic systems, namely the 5-HT2a receptor. Common antipsychotic drugs and hallucinogens used for mental health treatment are known to bind to the 5-HT2a receptor, and activation of this receptor is believed to lead to a downstream improvement of behavioral and emotional symptoms. One drug that has binding affinity for the 5-HT2a receptor is N,N,N-Trimethyltryptamine (TMT), however, there is limited research on the effects of TMT molecularly and behaviorally. Our collaborator, Dr. Andrew Jones, produced TMT in his laboratory, an analog of psilocybin that is structurally similar to another hallucinogen, dimethyltryptamine (DMT). In this study, molecular Gq-dependent calcium flux assays were performed using fluo-4 calcium sensitive dye, which allowed for the observation of fluorescence if TMT binds to and activates the 5-HT2a receptor. Behaviorally, 9 rats in 3 cohorts underwent head twitch response assessments, which are used as indicators of 5-HT2a binding. Data was collected from a magnetometer and recorded with a camera immediately following treatment. Due to the structural similarities between TMT and DMT, we expect that TMT will bind to the 5-HT2a receptor on the Gq-dependent calcium flux assay and will induce a significant increase in head twitches in a dose-dependent manner. Results from the head twitch response found no statistically significant effect of TMT dosage on head twitch response. Future directions include increasing sample size to increase the statistical power of the behavioral data and assessing TMT’s binding affinity to other serotonin receptors, specifically 5-HT2b and 5-HT2c. This project is relevant to my future career, as I plan on entering the field of medicine where exploration of new treatments for mental health disorders is prevalent.
Author(s): Sarah Quinlivan, Kinesiology and Public Health Major
Advisor(s): Matthew McMurray, Department of Psychology
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