The psychedelic, DOI, increases dopamine release in nucleus accumbens to predictable rewards and reward cues
bioRxiv (Cold Spring Harbor Laboratory) March 31, 2024 David Martin, Á.v. Delgado, Donna J. Calu preprint
Psychedelics may help treat neuropsychiatric disorders by disrupting entrenched associations and promoting new learning. In rats performing a Pavlovian task where sequential cues predict rewards, the psychedelic DOI (a 5-HT2A/2C agonist) increased dopamine signaling in the nucleus accumbens core to rewards and to cues immediately preceding them, but not to more distal predictive cues. This elevated dopamine occurred independently of changes in reward value and supports increased prediction error signaling. The findings suggest psychedelics could engage error-driven learning mechanisms to disrupt or form new associations.