Adolescent exposure to the psychedelic 25C-NBOMe in rats induces lasting competitive avoidance through disrupted hippocampal–prefrontal synchrony
Zhi-Peng Yu, Zhong-Yu Zhang, Qiong Li, Y Hu, Ting Zhang, Xiaoqin Zhang, Zi Wang, Wen-Hua Zhou, Haowei Shen
Nature Neuroscience July 20, 2026 DOI: 10.1038/s41593-026-02369-y (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Male Sprague-Dawley rats |
| Interventions | 25C-NBOMe Chemogenetic activation Chemogenetic inhibition |
| Topics | Serotonin |
| Keywords | Orbitofrontal cortex Hippocampus Ventral tegmental area Prosocial behavior Prefrontal cortex Ventral striatum Vulnerability computing Social relation Glutamate receptor Social grooming Anterior cingulate cortex Competition biology |
| Key findings | Adolescent, but not adult, exposure to 25C-NBOMe induced lasting competitive avoidance in male rats, predicted by reduced vHPC-OFC theta coherence. Chemogenetic activation of this projection normalized the behavior, while inhibition induced it in controls. |
Abstract
Psychedelics, known for prosocial effects and therapeutic potential in psychiatry, are often first used during adolescence, yet their enduring impact on social behavior and its underlying circuits remain unclear. Here we show that repeated exposure to the serotonergic psychedelic drug 25C-NBOMe during adolescence, but not exposure in adulthood, induced lasting competitive avoidance in male Sprague-Dawley rats-the most prominent change among several interrelated social behaviors and one that was not a collateral effect of altered sociability or social dominance. Multisite recordings revealed disrupted default mode network (DMN) synchrony, with reduced theta band coherence between the ventral hippocampus (vHPC) and the orbitofrontal cortex (OFC) most strongly predicting this behavioral change. Chemogenetic activation of the vHPC → OFC projection normalized the avoidance behavior in drug-exposed rats, whereas chemogenetic inhibition induced it in controls. These findings indicate that the vulnerability of DMN synchrony to psychedelics during adolescence can durably reshape adult social functioning.
Comparable studies
Other preclinical and animal studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cites 24
- The Brain's Default Mode Network Annual Review of Neuroscience May 4, 2015
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- The default mode network in cognition: a topographical perspective Nature Reviews Neuroscience July 5, 2021
- 20 years of the default mode network: A review and synthesis Neuron May 10, 2023
- The default mode network: where the idiosyncratic self meets the shared social world Nature Reviews Neuroscience January 22, 2021
and 19 more in the library