Effects of psilocybin on uncertain punishment learning.

Psilocybin alters how rats suppress actions when facing a conflict between seeking reward and avoiding punishment, but the effect depends on timing. During learning, psilocybin increased behavioral suppression in female rats as they learned that a risky action could lead to punishment. After the reward-punishment associations were already learned, psilocybin decreased behavioral suppression in both male and female rats. These divergent effects suggest that psilocybin's influence on approach-avoidance conflict changes depending on whether the conflict is being learned or has already been learned, which may relate to its therapeutic action in mood disorders.

Study at a glance

Abstract

Psilocybin may provide a useful treatment for mood disorders including anxiety and depression but its mechanisms of action for these effects are not well understood. While recent preclinical work has begun to assess psilocybin's role in affective behaviors through innate anxiety or fear conditioning, there is scant evidence for its role in conflict between reward and punishment. The current study was designed to determine the impact of psilocybin on the learning of reward-punishment conflict associations, as well as its effects after learning, in male and female rats. We utilized a chained schedule of reinforcement that involved execution of safe and risky reward-guided actions under uncertain punishment. Different patterns of behavioral suppression by psilocybin emerged during learning versus after learning of risky action-reward associations. Psilocybin increased behavioral suppression in female rats as punishment associations were learned. After learning, psilocybin decreased behavioral suppression in both sexes. Thus, psilocybin produces divergent effects on action suppression during approach-avoidance conflict depending on when the conflict is experienced. This observation may have implications for its therapeutic mechanism of action.