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Authors & Affiliations
Daniela Domingues, Clara Nguyen, Gabrielle Michon, Eric Burguière
Abstract
The discovery of LSD launched a new era of psychedelic research. The number of clinical trials is consistently increasing since psychedelics' sustained therapeutic effects seem to be promising in the reduction of symptoms of various neuropsychiatric disorders. In humans, the acute neuronal effect of psychedelics is often measured by fMRI and EEG signals and their behaviour through subjective questionnaires. In rodents, behavioural testing is much more precise. However, fMRI is only possible in anaesthetized animals which poses its own limitations.
Researchers have circumvented this challenge by combining clearing and immunohistochemistry techniques to stain immediately early genes (proxies of neuronal activity) induced by psychedelics at the acute level. So far, there are maps of the whole mouse brain after the administration of psilocybin (Davoudian et al., 2023; Rijsketic et al., 2023) and ketamine (Davoudian et al., 2023; Datta et al., 2023) but not after LSD.
The main goal of this project is to provide the field with an unbiased whole mouse brain mapping of the acute effect of different doses of LSD as well as behaviour quantifications. LSD is a dose-dependent drug hence modulating brain regions differently depending on its dosage. Behaviourally, LSD induces a locomotion bell shape dose-response as well as exploratory behaviours such as rearing. By assessing the behavioural and neuronal activity of mice administered with a wide range of LSD doses we aim to find a low and a high dose for future studies.