A44: The Effects of Psilocybin on Decision Making and Motivation

There has been a resurgence in research regarding the therapeutic potential of hallucinogenic psilocybin. Although this research is promising, much is unknown about how psilocybin impacts behavior from a pharmacological perspective. It is established that psilocybin is a serotonergic agonist with affinities for several different serotonin receptors; binding affinity data indicate that psilocybin has a high affinity for the 5HT-2A receptor. Serotonin receptors, including 5HT-2A, are densely located throughout the mesocorticolimbic system, which has major implications in decision-making and motivation-related behaviors. Thus implying that psilocybin may have significant effects on these pathways. This study investigated whether psilocybin impacts decision-making in probability and delay discounting tasks in male and female rats. In the probability discounting task, subjects chose between a certain, small reward and a risky, large reward that occurred with declining probability across days of testing. In the delay discounting task, animals chose between a small, immediate reward or a large reward delivered after increasingly longer delays across days of testing. Animals were administered 1mg/kg psilocybin via gavage prior to behavioral testing. Using repeated measures ANOVA (fitted data), results show that animals treated with psilocybin perform in a comparable manner to control subjects in probabilistic and delay discounting tasks. These results indicate that the pharmacology of psilocybin impacts decision making pathways in a manner contrary to our original hypothesis. This might be explained by the complex pharmacology of psilocybin simultaneously agonizing 5HT-2A and 5HT-2C receptors. To determine if psilocybin affects motivation, subjects were further tested on a progressive ratio task, in which the number of lever presses required to obtain reward increases with each subsequent reward. We found no effect of psilocybin on total responses or breakpoints, therefore implying that psilocybin does not affect motivation. Future directions will investigate the impact of chronic variable stress (CVS) on this paradigm.

Authors: Grace Petryk, Alexia Zylko

Advisors: J. Andrew Jones, Chemical, Paper, and Bioengineering, Matthew McMurray, Psychology