title: Neurovascular and neuroimaging effects of the hallucinogenic serotonin receptor agonist psilocin in the rat brain.
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.
authors.affiliation: Department of Psychology, University of Sheffield, Western Bank, Sheffield S10 2TP, UK; Cancer Research UK & Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK. Electronic address: spain.aisling@gmail.com.
authors.forename: Aisling
authors.initials: A
authors.lastname: Spain
authors.affiliation: Department of Psychology, University of Sheffield, Western Bank, Sheffield S10 2TP, UK; Cancer Research UK & Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK. Electronic address: c.howarth@sheffield.ac.uk.
authors.forename: Clare
authors.initials: C
authors.lastname: Howarth
authors.affiliation: Cancer Research UK & Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK. Electronic address: alexandr.khrapichev@oncology.ox.ac.uk.
authors.forename: Alexandre A
authors.initials: AA
authors.lastname: Khrapitchev
authors.affiliation: Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK. Electronic address: trevor.sharp@pharm.ox.ac.uk.
authors.forename: Trevor
authors.initials: T
authors.lastname: Sharp
authors.affiliation: Cancer Research UK & Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK. Electronic address: nicola.sibson@oncology.ox.ac.uk.
authors.forename: Nicola R
authors.initials: NR
authors.lastname: Sibson
authors.affiliation: Department of Psychology, University of Sheffield, Western Bank, Sheffield S10 2TP, UK. Electronic address: c.martin@sheffield.ac.uk.
authors.forename: Chris
authors.initials: C
authors.lastname: Martin
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D001931:Brain Mapping; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004567:Electrodes, Implanted; D006213:Hallucinogens / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D008279:Magnetic Resonance Imaging; D008297:Male; D010100:Oxygen / Q000097:blood; D011562:Psilocybin / Q000031:analogs & derivatives* / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D055698:Touch Perception / Q000187:drug effects / Q000502:physiology; D014738:Vibrissae / Q000502:physiology
chemical_list: D006213:Hallucinogens; D011562:Psilocybin; C009105:psilocin; D010100:Oxygen
keywords: Cerebral haemodynamics; Functional MRI; Neurovascular; Pharmacological MRI; Psilocin; Psilocybin