The psychedelic, DOI, increases dopamine release in nucleus accumbens to predictable rewards and reward cues
David Martin, Á.v. Delgado, Donna J. Calu
bioRxiv (Cold Spring Harbor Laboratory) March 31, 2024 preprint DOI: 10.1101/2024.03.29.587390 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study |
|---|---|
| Population | Rats |
| Topics | Addiction |
| Keywords | Nucleus accumbens Reward system Cognitive psychology Dopamine agonist Dopaminergic |
| Key findings | The psychedelic DOI increases dopamine signaling to rewards and proximal reward cues in the nucleus accumbens core, consistent with enhanced prediction error signaling. |
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.
Comparable studies
Other preclinical and animal studies on addiction, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics reopen the social reward learning critical period Mice | 2023 | Experimental study in mice | |
| Glial Cell Line-Derived Neurotrophic Factor Mediates the Desirable Actions of the Anti-Addiction Drug Ibogaine against Alcohol Consumption Rats | 2005 | Experimental study | |
| Effects of ibogaine on acute signs of morphine withdrawal in rats: independence from tremor. Morphine-dependent rats | 1992 | Randomized controlled trial | |
| Structure-based discovery of conformationally selective inhibitors of the serotonin transporter. Mice | 2023 | Computational docking and experimental validation | |
| Reinforcing Effects of MDMA (‘Ecstasy’) in Drug-Naive and Cocaine-Trained Rats Rats | 2001 | Experimental study |
Citations in the library
Cited by 2
- Moving beyond 5-HT2A: language models map neurotransmitter receptors to experiential semantics. Psychopharmacology September 29, 2026
- Differential effects of psilocybin derivatives on fentanyl-induced conditioned place preference in male and female mice. Journal of Psychopharmacology August 30, 2026
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