PT  - JOURNAL ARTICLE
AU  - Andrea I. Luppi
AU  - Justine Y. Hansen
AU  - Ram Adapa
AU  - Robin L. Carhart-Harris
AU  - Leor Roseman
AU  - Daniel Golkowski
AU  - Andreas Ranft
AU  - Rüdiger Ilg
AU  - Denis Jordan
AU  - Alexander R. D. Peattie
AU  - Anne E. Manktelow
AU  - Draulio B. de Araujo
AU  - Stefano L. Sensi
AU  - Adrian M. Owen
AU  - Lorina Naci
AU  - David K. Menon
AU  - Bratislav Misic
AU  - Emmanuel A. Stamatakis
TI  - Mapping Pharmacologically-induced Functional Reorganisation onto the Brain’s Neurotransmitter Landscape
AID  - 10.1101/2022.07.12.499688
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.07.12.499688
4099  - http://biorxiv.org/content/early/2022/07/13/2022.07.12.499688.short
4100  - http://biorxiv.org/content/early/2022/07/13/2022.07.12.499688.full
AB  - To understand how pharmacological interventions can exert their powerful effects on brain function, we need to understand how they engage the brain’s rich neurotransmitter landscape. Here, we bridge microscale molecular chemoarchitecture and pharmacologically-induced macroscale functional reorganisation, by relating the regional distribution of 18 neurotransmitter receptors and transporters obtained from Positron Emission Tomography, and the regional changes in functional MRI connectivity induced by 7 different mind-altering drugs including anaesthetics, psychedelics, and cognitive enhancers. Our results reveal that psychoactive drugs exert their effects on brain function by engaging multiple neurotransmitter systems. Intriguingly, the effects of both anaesthetics and psychedelics on brain function, though opposite, are organised along hierarchical gradients of brain structure and function. Finally, we show that regional co-susceptibility to pharmacological interventions recapitulates co-susceptibility to disorder-induced structural alterations. Collectively, these results highlight rich statistical patterns relating molecular chemoarchitecture and drug-induced reorganisation of the brain’s functional architecture.Competing Interest StatementRCH reports receiving scientific advisory fees in the last 2 years from: Entheon Biomedical and Beckley Psytech. All other authors report no conflicts of interest.