Neurovascular and neuroimaging effects of the hallucinogenic serotonin receptor agonist psilocin in the rat brain

Psilocin, the active metabolite of psilocybin, causes region-specific changes in brain activity measured by pharmacological MRI (phMRI). In rats, a high dose (2 mg/kg) increased phMRI signals in olfactory, limbic, and visual areas while decreasing signals in somatosensory and motor cortices. However, direct comparison of neuronal activity (local field potentials) and blood flow showed that psilocin reduced neuronal responses to sensory stimuli but enhanced the accompanying blood flow response. This dissociation indicates that phMRI signal changes reflect not only neuronal activity but also drug-induced alterations in neurovascular coupling, complicating the interpretation of hemodynamic neuroimaging data in pharmacological studies.

Study at a glance

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.