title: Selective serotonin 5-HT1A receptor biased agonists elicitdistinct brain activation patterns: a pharmacoMRI study.
abstract: Serotonin 1A (5-HT1A) receptors are involved in several physiological and pathological processes and constitute therefore an important therapeutic target. The recent pharmacological concept of biased agonism asserts that highly selective agonists can preferentially direct receptor signaling to specific intracellular responses, opening the possibility of drugs targeting a receptor subtype in specific brain regions. The present study brings additional support to this concept thanks to functional magnetic resonance imaging (7 Tesla-fMRI) in anaesthetized rats. Three 5-HT1A receptor agonists (8-OH-DPAT, F13714 and F15599) and one 5-HT1A receptor antagonist (MPPF) were compared in terms of influence on the brain blood oxygen level-dependent (BOLD) signal. Our study revealed for the first time contrasting BOLD signal patterns of biased agonists in comparison to a classical agonist and a silent antagonist. By providing functional information on the influence of pharmacological activation of 5-HT1A receptors in specific brain regions, this neuroimaging approach, translatable to the clinic, promises to be useful in exploring the new concept of biased agonism in neuropsychopharmacology.
authors.affiliation: Université Claude Bernard Lyon 1, Centre de Recherche en Neurosciences de Lyon, CNRS, INSERM, Lyon, France.|Hospices Civils de Lyon, Lyon, France.
authors.forename: G
authors.initials: G
authors.lastname: Becker
authors.affiliation: CERMEP - Imagerie du vivant, Lyon, France.
authors.forename: R
authors.initials: R
authors.lastname: Bolbos
authors.affiliation: CERMEP - Imagerie du vivant, Lyon, France.
authors.forename: N
authors.initials: N
authors.lastname: Costes
authors.affiliation: CERMEP - Imagerie du vivant, Lyon, France.
authors.forename: J
authors.initials: J
authors.lastname: Redouté
authors.affiliation: Neurolixis Inc., Dana Point, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Newman-Tancredi
authors.affiliation: Université Claude Bernard Lyon 1, Centre de Recherche en Neurosciences de Lyon, CNRS, INSERM, Lyon, France.|Hospices Civils de Lyon, Lyon, France.|CERMEP - Imagerie du vivant, Lyon, France.
authors.forename: L
authors.initials: L
authors.lastname: Zimmer
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D001931:Brain Mapping; D008279:Magnetic Resonance Imaging; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D058829:Serotonin 5-HT1 Receptor Antagonists