Effect of Psilocin on Extracellular Dopamine and Serotonin Levels in the Mesoaccumbens and Mesocortical Pathway in Awake Rats
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Psilocin (3-[2-(dimethylamino)ethyl]-1H-indol-4-ol) is a hallucinogenic component of the Mexican mushroom Psilocybe mexicana and a skeletal serotonin (5-HT) analogue. Psilocin is the active metabolite of psilocybin (3-[2-(dimethylamino)ethyl]-1H-indol-4-yl dihydrogen phosphate). In the present study, we examined the effects of systemically administered psilocin on extracellular dopamine and 5-HT concentrations in the ventral tegmental area (VTA), nucleus accumbens, and medial prefrontal cortex of the dopaminergic pathway in awake rats using in vivo microdialysis. Intraperitoneal administration of psilocin (5, 10 mg/kg) significantly increased extracellular dopamine levels in the nucleus accumbens. Psilocin did not affect the extracellular 5-HT level in the nucleus accumbens. Conversely, systemic administration of psilocin (10 mg/kg) significantly increased extracellular 5-HT levels in the medial prefrontal cortex of rats, but dopamine was decreased in this region. However, neither extracellular dopamine nor 5-HT levels in the VTA were altered by administration of psilocin. Behaviorally, psilocin significantly increased the number of head twitches. Thus, psilocin affects the dopaminergic system in the nucleus accumbens. In the serotonergic system, psilocin contribute to a crucial effect in the medial prefrontal cortex. The present data suggest that psilocin increased both the extracellular dopamine and 5-HT concentrations in the mesoaccumbens and/or mesocortical pathway.
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Rat microdialysis studies showed that psilocin (10 mg/kg) evoked a transient 40% increase in interstitial dopamine levels.
“Rat microdialysis studies showed that psilocin (8) (10 mg/kg) evoked a transient 40% increase in interstitial dopamine levels [97]”
From Molecular and Functional Imaging Studies of Psychedelic Drug Action in Animals and Humans. (2021) · cites this paper as [97]
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Psilocybin Combines Rapid Synaptogenic And Anti-Inflammatory Effects In VitroPreprint
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The therapeutic potential of psilocybin beyond psychedelia through shared mechanisms with ketamine
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“Preclinical studies have demonstrated increased dopamine release in mesolimbic circuits and altered striatal connectivity following psilocybin administration [178, 179].”
Wittenkeller, L. M., Gudelsky, G. A., Winhusen, T. M., & Amato, D. (2025) · British Journal of Pharmacology · doi:10.1111/bph.70181 · Cited by 7 · see citing works
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Martin, D. A., Delgado, A. M., & Calu, D. J. (2024) · Neuropsychopharmacology · doi:10.1038/s41386-024-01912-4 · Cited by 5 · see citing works
“Psychedelics increase tonic striatal DA levels in humans [34] and in rodents [35].”
The effect of psilocin on neurotransmitters release in the claustrum and on rat behavior
Kościuk, Z., Szpręgiel, I., Bysiek, A., & Gołembiowska, K. (2026) · Pharmacological Reports · doi:10.1007/s43440-025-00817-3 · Cited by 3 · see citing works
“The paradoxical attenuation of DA release at higher psilocin doses (500 µM) likely reflects local activation of inhibitory 5-HT1A recep - tors or compensatory circuit-level adaptations within the claustrum, which in turn dampen excitatory influences on dopaminergic signaling [ 28 ].”
Ivan, V. E., Tomàs‐Cuesta, D. P., Esteves, I. M., Luczak, A., Mohajerani, M. H., McNaughton, B. L., & Gruber, A. J. (2024) · European Journal of Neuroscience · doi:10.1111/ejn.16558 · Cited by 3 · see citing works
“Rodent studies have likewise found that psilocybin or its active form psilocin can affect dopamine, serotonin, glutamate and gamma-aminobutyric acid (GABA) levels in the frontal cortex and/or striatum (Sakashita et al., 2015; Wojtas et al., 2022).”
Molecular brain imaging of psychedelic action
Cumming, P. D., Egger, K., & Knudsen, G. M. (2025) · International review of neurobiology · doi:10.1016/bs.irn.2025.02.005 · Cited by 3 · see citing works
McCoy, K., Reed, F. M., Conn, K., & Foldi, C. J. (2025) · Physiology & Behavior · doi:10.1016/j.physbeh.2025.114957 · Cited by 3 · see citing works
“Psilocybin has been shown to increase extracellular dopamine (DA) in the ventral striatum of humans [141] and rats [115], although neither the neuronal drivers nor behavioural consequences of this have been investigated.”
InfluentialGalstyan, D. S., Krotova, N. A., Lebedev, A. S., Kotova, M. M., Martynov, D. D., Golushko, N. I., Perederiy, A. S., Zhukov, I. S., Rosemberg, D. B., Lim, L. W., et al. (2025) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2025.177312 · Cited by 3 · see citing works
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“50,51 Interestingly, 5-HT2A receptors are also located on some c -aminobutyric acid neurons.”
Wu, Y., Ran, J., Mo, J., & Wang, J. (2025) · Addiction Biology · doi:10.1111/adb.70063 · Cited by 1 · see citing works
“Psilocin mediates its psychedelic effects via direct agonism of 5-HT receptors, with concomitant increases in extracellular 5-HT concentrations within mesocorticolimbic pathways [11].”
Domi, A., Lucente, E., Cadeddu, D., Bengtsson, N., Smedler, E., & Adermark, L. (2026) · Neuropharmacology · doi:10.1016/j.neuropharm.2026.110854 · Cited by 1 · see citing works
Classic psychedelics in obsessive–compulsive disorder: a circuit-based framework
Ali, S. S., Carhart-Harris, R. L., & Sieg, K. G. (2026) · Nature Mental Health · doi:10.1038/s44220-026-00626-4 · Cited by 1 · see citing works
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Lawrence, D. W., Battista, A. P. D., & Hutchison, M. G. (2025) · Psychoactives · doi:10.3390/psychoactives4030022 · Cited by 1 · see citing works
“…while psilocybin’s effects are primarily attributed to serotonergic mechanisms, preclinical evidence also suggests it may modulate dopaminergic pathways, specifically increasing extracellular dopamine in the nucleus accumbens, which could also contribute to observed behavioral improvements [51].”
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Mycotherapeutics Affecting Dopaminergic Neurotransmission to Exert Neuroprotection
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The 5-HT1B Autoreceptor's Role in Emotional Processing in Relation to Acute Psilocybin ExperiencesPreprint
Malinak, M., & Beach, K. (2025) · SSRN Electronic Journal · doi:10.2139/ssrn.5377073
Potencial terapéutico de la psilocibina en neuropsiquiatría: una revisión narrativa
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Medicinal Mushrooms and Mental Disorders: How Mushrooms Affect Anxiety and Depression
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Trip killers: Addressing a critical knowledge gap in psychedelic research
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Psychedelics and Reward Processing: Before and After the 1970 Controlled Substances Act
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Moving beyond 5-HT2A: language models map neurotransmitter receptors to experiential semantics
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- Authors
- Sakashita, Y., Abe, K., Katagiri, N., Kambe, T., Saitoh, T., Utsunomiya, I., Horiguchi, Y., & Taguchi, K.
- Affiliations
- Showa Pharmaceutical University (JP)
- Ohu University (JP)
- Nihon Pharmaceutical University (JP)
- ORCID
- Abe, Kenji
- Venue
- Biological ^|^ Pharmaceutical Bulletin
- Publisher
- Pharmaceutical Society of Japan
- Published
- 2015
- Volume
- 38
- Issue
- 1
- Pages
- 134-138
- ISSN
- 0918-6158 (ISSN-L)
- 1347-5215
- OpenAlex
- W2079092936
- Cited by
- 81
- References
- 33
- Citations by year
- 2026: 7 · 2025: 18 · 2024: 12 · 2023: 13 · 2022: 7 · 2021: 8 · 2020: 5 · 2019: 2 · 2018: 4 · 2016: 4 · 2015: 1
- FWCI
- 1.97
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Biological and Pharmaceutical Bulletin (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- psilocin, psilocybin, hallucinogens, extracellular dopamine, serotonin, mesocortical pathway, ventral tegmental area, nucleus accumbens, medial prefrontal cortex, head twitches, serotonin receptor agonists
- MeSH terms
- Animals, Dopamine, Hallucinogens, Male, Nucleus Accumbens, Psilocybin, Serotonin, Rats, Wistar, Prefrontal Cortex, Ventral Tegmental Area
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