Neurovascular and neuroimaging effects of the hallucinogenic serotonin receptor agonist psilocin in the rat brain. (December 2015)

• Record Type: Journal Article
• Authors: Spain, Aisling; Howarth, Clare; Khrapitchev, Alexandre A.; Sharp, Trevor; Sibson, Nicola R.; Martin, Chris
• Is Part Of: Neuropharmacology. Volume 99(2015)
• Page Start: 210
• Page End: 220
• Publication Date: 2015-12
• Subjects: Psilocin -- Psilocybin -- Pharmacological MRI -- Functional MRI -- Neurovascular -- Cerebral haemodynamics; AUC area under the curve -- BOLD blood oxygen level dependent -- CBF cerebral blood flow -- ISI inter-stimulus-interval -- LC locus coeruleus -- LFP local field potential -- phMRI pharmacological MRI -- ROI region of interest -- SSRI selective serotonin reuptake inhibitor; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2015.07.018
• Languages: English
• ISSNs: 0028-3908

Abstract

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. Highlights: The pharmacological MRI (phMRI) response to psilocin is characterised in rats. Region specific increases and decreases in phMRI signals are observed. Underlying neuronal and haemodynamic changes are also measured in vivo . Evidence for altered neuronal-haemodynamic (neurovascular) coupling by psilocin. phMRI interpretation should consider neurovascular as well as neuronal drug effects.