Recent study of the hallucinogenic drug psilocybin points towards potential therapeutic benefits for serotonin-linked mood disorders, such as major depressive disorder and PMDD, a depressive disorder that is associated with women’s estrous cycles and the cycling of estradiol. The primary mechanism of action of psilocybin is agonistic on the 5HT2A receptor. Estradiol has been shown to increase expression of 5HT2A receptors leading to increased receptor density in various brain regions. The potential link between rising and falling levels of estradiol and psilocybin efficacy at the 5HT2A receptor will be studied by administering psilocybin to female rats while in proestrus, diestrus, and anestrus. An anestrus state will be achieved by the administration of birth control. A 3.5mg dose of medroxyprogesterone acetate (MPA) will be subcutaneously injected weekly. To assess efficacy of psilocybin, head twitch frequency, a behavior associated with hallucinogenic drug use, will be measured. After euthanasia, a Western Blot analysis will be performed on brain tissue to assess 5HT2A receptor density during different stages of the estrous cycle. It is expected that during proestrus, head twitch frequency and 5HT2A receptor density will be higher than during diestrus and anestrus phases. Preliminary results reflect a potentially conflicting association between estrous cycle and head-twitch response. While previous work has shown a link between psilocybin and the 5HT2A receptor, as well as estradiol levels and expression of the 5HT2A receptor, this work intends to connect the combined actions of psilocybin and estradiol at this receptor and possible behavioral effects, while also piloting birth control as a novel and minimally invasive way of inducing anestrus conditions.
Authors: Page, A., Heitkamp, M., Wilson, M., Powell Á., Feist, D.
Advisors: M.S McMurray, Psychology. J.A Jones, Chemical, Paper, and Biomedical Engineering
Graduate Advisor: Oscar Sandoval, Psychology. Brianna Roberts, Psychology
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