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.

Psychedelics

“…administered to rats evoked phMRI signal increases in a number of regions, including olfactory and limbic areas and elements of the visual system (Spain et al, 2015). LFP amplitude in response to sensory stimuli was decreased by psilocin administration, concurrently with enhanced CBF.…”

“…The alteration in neurovascular coupling reported by Spain et al (2015) might explain, in part, the apparent discrepancy between fMRI and PET findings of decreased CBF (Carhart-Harris et al, 2012) and increased glucose metabolism (Vollenweider et al, 1997b;Gouzoulis-Mayfrank et al, 1999) in human studies with psilocybin and related drugs.…”

Acute effects of systemic inflammation upon neurovascular unit and cerebrovascular function.

“…These effects became evident at 6 hours after LPS administration, although similar (non-significant) trends could be observed at the 4 hour time point. It is difficult to assess why significant effects of altered cerebrovascular function are primarily driven by a specific stimulation frequency, although stimulation dependent effects have been previously reported in the literature [40, 41]. Our results suggest the 5Hz stimulation frequency to be particularly salient at driving this effect, and it has been previously reported that in anaesthetised animals this frequency is most effective in driving somatosensory neurovascular responses [41].…”

Deciphering the scopolamine challenge rat model by preclinical functional MRI

“…injection increased the BOLD contrast in the frontal (orbital) cortex and olfactory nuclei while it was absent after BSCO injection [11]. These diverging results highlight the difficulty interpreting preclinical pharmaco-MRI data [12] complicated by the use of different anesthetic regimes [13] that can introduce potential confounds [14].…”