Psilocybin reduces alcohol self-administration via selective left nucleus accumbens activation in rats
Jérôme Jeanblanc, Romain Bordy, Grégory Fouquet, Virginie Jeanblanc, Mickaël Naassïla
Brain May 4, 2024 DOI: 10.1093/brain/awae136 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Male Long Evans rats |
| Interventions | Psilocybin Ketanserin |
| Dose | 1 mg/kg intraperitoneal psilocybin; 0.15 μg intra-left nucleus accumbens psilocybin; 0.3 μg intra-left nucleus accumbens ketanserin |
| Topics | Psilocybin |
| Keywords | Nucleus accumbens Self-administration Alcohol Pharmacology Hallucinogen |
| Citations | 10 |
| Key findings | Psilocybin reduces ethanol self-administration by 50% in rats through the 5-HT2A receptor in the left nucleus accumbens, possibly via increased D2R expression. |
Abstract
Abstract The use of psilocybin to treat alcohol use disorder is very promising, but its mechanisms of action remain poorly understood. We combined behavioural, pharmacological and gene expression analyses to decipher the mechanisms of action of psilocybin, for the first time, when injected into the brain. Male Long Evans rats underwent chronic operant ethanol self-administration before testing the effect of intraperitoneal psilocybin or directly within the nucleus accumbens core or the ventral tegmental area. Transcripts from the dopaminergic system were quantified in the nucleus accumbens and prefrontal cortex. Psilocybin significantly reduced (by 50%) ethanol self-administration when injected 4 h before the session either intraperitoneally (1 mg/kg) or directly within the left nucleus accumbens (0.15 μg) but not the right nucleus accumbens or the left ventral tegmental area. The effect of intraperitoneal injection of psilocybin was prevented by intra-left nucleus accumbens injection of 0.3 μg of the 5-HT2A receptor antagonist ketanserin. In rats that self-administered ethanol but not in those self-administering saccharin, dopamine D2 receptor (D2R) mRNA was increased in both the nucleus accumbens and the prefrontal cortex by psilocybin, while dopamine D1 receptor mRNA was increased only in the prefrontal cortex. As in humans, psilocybin reduced ethanol self-administration in rats through the 5-HT2A receptor within the left nucleus accumbens, possibly through increased D2R expression. Our results open unexpected perspectives regarding the hemispheric lateralization of psychedelic effects.
Comparable studies
Other preclinical and animal studies on psilocybin, 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 | |
| Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice Mice | 2021 | Experimental study | |
| Psychedelics reopen the social reward learning critical period Mice | 2023 | Experimental study in mice | |
| Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. C57BL/6J mice | 2020 | Experimental study with dose-response experiments | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study |
Citations in the library
Cited by 11
- The Emergence of Psilocybin in Psychiatry and Neuroscience Pharmaceuticals April 9, 2025
- 5-HT2A receptors shape whole-brain monoaminergic coherence in male mice. Progress in Neuro-Psychopharmacology and Biological Psychiatry July 13, 2025
- High dose of psilocybin induces acute behavioral changes without inducing conditioned place preference in Sprague-Dawley rats Journal of Psychopharmacology September 22, 2025
- Psychedelics as pharmacotherapeutics for substance use disorders: A scoping review on clinical trials and perspectives on underlying neurobiology British Journal of Pharmacology September 2, 2025
- Psilocybin administered following extinction sessions does not affect subsequent cocaine cue reinstatement in male and female rats and mice. Neuroscience November 1, 2024
and 6 more in the library
Cites 18
- Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin Proceedings of the National Academy of Sciences January 23, 2012
- Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder JAMA Psychiatry August 24, 2022
- Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Scientific Reports October 13, 2017
- Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor Elife October 25, 2018
- Dynamical exploration of the repertoire of brain networks at rest is modulated by psilocybin. Neuroimage May 25, 2019
and 13 more in the library