Abstract #0597

Use of Pharmacological MRI (phMRI) to understand the mechanisms leading to convergent procognitive effects of 5-HT6 serotonergic receptors agonist (EMD-386088) and antagonist (SB-271046).

Willy Gsell¹, Rachel Asselot², Nicolas Delcroix³, Uwe Himmelreich¹, Valentine Bouet², and François Dauphin²

¹Biomedical MRI group, KU Leuven, Leuven, Belgium, ²GMPc (Groupe Mémoire et Plasticité comportementale), University of Caen-Normandie, Caen, France, ³CNRS UMS3408, GIP CYCERON, Caen, France

Either blocking or activating 5HT6 receptors (5-HT6R), respectively with antagonists or agonists, exert beneficial cognitive effects. Through phMRI, we demonstrated for the first time the similarities and discrepancies in the brain activation induced by an agonist and an antagonist of 5-HT6R. Both drugs similarly activate cortices and hippocampus. SB-271046 positively activates a network including the medio-dorsal raphe while EMD-386088 activates the rostral dorsal raphe. The different patterns of activation elicited in brain regions such as the habenula and the MG/DG nuclei (for SB-271046), or the amygdala and substantia nigra (for EMD-386088) supports different interactions with polysynaptic pathways.

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