The Effect of Acute and Chronic Administration of Fluoxetine on R−(−)− DOI Induced Head Twitch Response in Swiss-Webster Mice

Abstract ID 96292 Poster Board 525 Psychedelics are a class of substances characterized by their psychoactive properties produced through the primary action of the serotonin system, specifically at the serotonin 2A receptor (5-HT2aR). Recent clinical research has shown efficacy for psychedelic use in treatment-resistant depression, with psilocybin receiving breakthrough status from the FDA. Although there has been extensive work showing the success of psychedelic use for treatment of depression, many studies evaluating this relationship exclude subjects with previous or current Selective Serotonin Reuptake Inhibitor (SSRI) use due to limited understanding of the possible interactions between the substances. The goal of this research is to understand how different dosing regimes of Fluoxetine, a highly prescribed SSRI, may impact the psychoactivity of a commonly studied psychedelic; 2,5-Dimethoxy-4-iodoamphetamine (DOI). Due to the differing mechanisms of action, it was hypothesized that there would be no influence of SSRI use on the psychoactive response from DOI. This was determined by evaluating the Head Twitch Response (HTR) in Swiss- Webster mice and creating dose response curves to determine the peak dose of DOI. HTR was evaluated after both acute and chronic administration of Fluoxetine. The first set of experiments evaluated the difference between acute administration of 10mg/kg Fluoxetine and 32mg/kg Fluoxetine when compared to saline. It was found that acute Fluoxetine administration resulted in no difference in the peak dose of DOI when compared to saline. It was also found that the acute high dose of Fluoxetine decreased the potency of DOI. When evaluating the effects of chronic Fluoxetine, it was found that there was no difference in the peak dose of DOI when compared to acute Fluoxetine and saline. These results suggest that there is no influence of chronic or acute SSRI use on the psychoactivity of psychedelics, and that it is possible and necessary to begin clinical trials involving participants with a history of antidepressant use.