Author:
Dukart Juergen,Holiga Štefan,Chatham Christopher,Hawkins Peter,Forsyth Anna,McMillan Rebecca,Myers Jim,Lingford-Hughes Anne R,Nutt David J,Merlo-Pich Emilio,Risterucci Celine,Boak Lauren,Umbricht Daniel,Schobel Scott,Liu Thomas,Mehta Mitul A,Zelaya Fernando O,Williams Steve C,Brown Gregory,Paulus Martin,Honey Garry D,Muthukumaraswamy Suresh,Hipp Joerg,Bertolino Alessandro,Sambataro Fabio
Abstract
AbstractApplication of metabolic magnetic resonance imaging measures such as cerebral blood flow in translational medicine is limited by the unknown link of observed alterations to specific neurophysiological processes. In particular, the sensitivity of cerebral blood flow to activity changes in specific neurotransmitter systems remains unclear. We address this question by probing cerebral blood flow in healthy volunteers using seven established drugs with known dopaminergic, serotonergic, glutamatergic and GABAergic mechanisms of action. We use a novel framework aimed at disentangling the observed effects to contribution from underlying neurotransmitter systems. We find for all evaluated compounds a reliable spatial link of respective cerebral blood flow changes with underlying neurotransmitter receptor densities corresponding to their primary mechanisms of action. The strength of these associations with receptor density is mediated by respective drug affinities. These findings suggest that cerebral blood flow is a sensitive brain-wide in-vivo assay of metabolic demands across a variety of neurotransmitter systems in humans.
Publisher
Cold Spring Harbor Laboratory