The psychedelic, DOI, increases dopamine release in nucleus accumbens to predictable rewards and reward cues

Summary

The psychedelic DOI enhances dopamine signaling in the nucleus accumbens specifically to rewards and their immediate cues, but not to more distant predictive cues. This increase in dopamine occurs independently of any changes in the perceived value of the rewards. These results suggest that psychedelics may boost prediction error signaling, which could help in creating new learning pathways or altering established associations in neuropsychiatric conditions.

Study at a glance

Abstract

Abstract Psychedelics produce lasting therapeutic responses in neuropsychiatric diseases suggesting they may disrupt entrenched associations and catalyze learning. Here, we examine psychedelic effects on dopamine signaling in the nucleus accumbens (NAc) core, a region extensively linked to reward learning, motivation, and drug-seeking. We measure phasic dopamine transients following acute psychedelic administration during well learned Pavlovian tasks in which sequential cues predict rewards. We find that the psychedelic 5-HT 2A/2C agonist, DOI, increases dopamine signaling to rewards and proximal reward cues but not to the distal cues that predict these events. We determine that the elevated dopamine produced by psychedelics to reward cues occurs independently of psychedelic-induced changes in reward value. The increased dopamine associated with predictable reward cues supports psychedelic-induced increases in prediction error signaling. These findings lay a foundation for developing psychedelic strategies aimed at engaging error-driven learning mechanisms to disrupt entrenched associations or produce new associations.

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