Neurovascular and neuroimaging effects of the hallucinogenic serotonin receptor agonist psilocin in the rat brain
Aisling Spain, Clare Howarth, Alexandre A. Khrapitchev, Trevor Sharp, Nicola R. Sibson, Chris Martin
Neuropharmacology July 18, 2015 DOI: 10.1016/j.neuropharm.2015.07.018 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled experiment Peer reviewed |
|---|---|
| Sample size | 18 |
| Population | Rats |
| Intervention | Psilocin |
| Dose | 2 mg/kg or 0.03 mg/kg i.v. |
| Topics | Psilocybin Serotonin |
| Keywords | Neuroimaging Somatosensory system |
| Citations | 45 |
| Key findings | Psilocin evokes region-specific phMRI signal changes in rats that confirm human data, but the hemodynamic responses reflect both altered neuronal activity and changes in neurovascular coupling. |
Abstract
The development of pharmacological magnetic resonance imaging (phMRI) has presented the opportunity for investigation of the neurophysiological effects of drugs in vivo. Psilocin, a hallucinogen metabolised from psilocybin, was recently reported to evoke brain region-specific, phMRI signal changes in humans. The present study investigated the effects of psilocin in a rat model using phMRI and then probed the relationship between neuronal and haemodynamic responses using a multimodal measurement preparation. Psilocin (2 mg/kg or 0.03 mg/kg i.v.) or vehicle was administered to rats (N=6/group) during either phMRI scanning or concurrent imaging of cortical blood flow and recording of local field potentials. Compared to vehicle controls psilocin (2 mg/kg) evoked phMRI signal increases in a number of regions including olfactory and limbic areas and elements of the visual system. PhMRI signal decreases were seen in other regions including somatosensory and motor cortices. Investigation of neurovascular coupling revealed that whilst neuronal responses (local field potentials) to sensory stimuli were decreased in amplitude by psilocin administration, concurrently measured haemodynamic responses (cerebral blood flow) were enhanced. The present findings show that psilocin evoked region-specific changes in phMRI signals in the rat, confirming recent human data. However, the results also suggest that the haemodynamic signal changes underlying phMRI responses reflect changes in both neuronal activity and neurovascular coupling. This highlights the importance of understanding the neurovascular effects of pharmacological manipulations for interpreting haemodynamic neuroimaging data.
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
Cited by 30
- Increased amygdala responses to emotional faces after psilocybin for treatment-resistant depression. Neuropharmacology December 27, 2017
- Models of psychedelic drug action: modulation of cortical-subcortical circuits Brain October 22, 2021
- Altered network hub connectivity after acute LSD administration NeuroImage: Clinical March 7, 2018
- Psychedelics Recruit Multiple Cellular Types and Produce Complex Transcriptional Responses Within the Brain EBioMedicine September 1, 2016
- Sex-specific effects of psychedelic drug exposure on central amygdala reactivity and behavioral responding. Translational Psychiatry April 8, 2023
and 25 more in the library
Cites 13
- Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer Archives of General Psychiatry September 7, 2010
- Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin Proceedings of the National Academy of Sciences January 23, 2012
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
- The pharmacology of psilocybin Addiction Biology October 1, 2002
- Psychedelics and the Human Receptorome PLoS One 2010
and 8 more in the library