The effect of psilocin on neurotransmitters release in the claustrum and on rat behavior.
Zuzanna Kościuk, Izabela Szpręgiel, Agnieszka Bysiek, Krystyna Gołembiowska
Pharmacological Reports February 1, 2026 DOI: 10.1007/s43440-025-00817-3 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vivo microdialysis experiment Peer reviewed |
|---|---|
| Population | Adult male Wistar Han rats |
| Interventions | Psilocin 25I-NBOMe |
| Dose | 100 or 500 µM for psilocin, 500 µM for 25I-NBOMe |
| Topics | Psilocybin |
| Keywords | 25i-nbome Claustrum Microdialysis Neurotransmission |
| Citations | 2 |
| Key findings | Psilocin produced a balanced excitatory–inhibitory neurochemical profile in the rat claustrum, whereas 25I-NBOMe drove a markedly more excitatory and less compensated pattern. |
Abstract
The claustrum, a subcortical structure densely expressing 5-hydroxytryptamine 2 A (5-HT2A) receptors, has been implicated in sensory integration, emotional regulation, salience, and attention. Despite its hypothesized involvement in the effects of serotonergic psychedelics, the neurochemical impact of these substances on claustral neurotransmission remains unexplored. This study aimed to investigate how psilocin — a tryptamine and the active metabolite of psilocybin — and 4-Iodo-2, 5-dimethoxy-N-(2-methoxybenzyl)phenethylamine (25I-NBOMe) — a phenethylamine and new psychoactive substance (NPS) — modulate extracellular neurotransmitter levels in the rat claustrum, as well as to examine their effects on wet dog shake behavior, a well-established proxy for hallucinogenic activity. Adult male Wistar Han rats were used for in vivo brain microdialysis experiments. Microdialysis probes were stereotaxically implanted into the claustrum. Rats received local administration of either psilocin (100 or 500 µM) or 25I-NBOMe (500 µM) through the microdialysis probe. Dialysate samples were collected and analyzed using high-performance liquid chromatography (HPLC) with electrochemical detection to quantify extracellular levels of dopamine (DA), noradrenaline (NA), serotonin (5-HT), glutamate (GLU), gamma-aminobutyric acid (GABA), and acetylcholine (ACh). A behavioral test defined as wet dog shakes (WDS) was conducted after drugs administration, to infer psychedelic-like activity. In vivo microdialysis performed in freely moving rats revealed that both substances markedly altered extracellular levels of DA, NA, 5-HT, GLU, GABA, and ACh. Psilocin, at both administered doses, was the only compound to significantly elevate NA and produced the most pronounced enhancement of cholinergic signaling across all neurotransmitter systems examined. By contrast, 25I-NBOMe induced a more substantial shift toward excitatory dominance, accompanied by the greatest increase in 5-HT release. Overall, psilocin generated a comparatively balanced excitatory–inhibitory neurochemical profile, reflecting its combined engagement of 5-HT2A and 5-HT1A receptors, whereas 25I-NBOMe produced an excitation-biased pattern consistent with its selective, high-affinity 5-HT2A agonism. These findings highlight the claustrum as a neurochemical convergence point for psychedelic action and demonstrate that psilocin engages this circuitry in a regulated, receptor-balanced manner, whereas 25I-NBOMe drives a markedly more excitatory and less compensated profile, underscoring their fundamentally distinct therapeutic and toxicological potentials. The online version contains supplementary material available at 10.1007/s43440-025-00817-3.
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 2
- Psilocybin produces amplified acute responses and sex-specific long-term increases in sensorimotor gating in the mGlu5 knockout mouse model of schizophrenia Neuropsychopharmacology July 18, 2026
- Blocking 5-HT2B receptors abolishes psilocybin’s efficacy in the rat forced swim test Journal of Psychopharmacology June 23, 2026
Cites 29
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Neuron July 5, 2021
- Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels Neuropsychopharmacology January 26, 2019
- Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors Science February 16, 2023
- Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice Proceedings of the National Academy of Sciences April 13, 2021
and 24 more in the library