title: Switching brain serotonin with oxytocin.
abstract: Serotonin (5-HT) and oxytocin (OXT) are two neuromodulators involved in human affect and sociality and in disorders like depression and autism. We asked whether these chemical messengers interact in the regulation of emotion-based behavior by administering OXT or placebo to 24 healthy subjects and mapping cerebral 5-HT system by using 2'-methoxyphenyl-(N-2'-pyridinyl)-p-[(18)F]fluoro-benzamidoethylpiperazine ([(18)F]MPPF), an antagonist of 5-HT1A receptors. OXT increased [(18)F]MPPF nondisplaceable binding potential (BPND) in the dorsal raphe nucleus (DRN), the core area of 5-HT synthesis, and in the amygdala/hippocampal complex, insula, and orbitofrontal cortex. Importantly, the amygdala appears central in the regulation of 5-HT by OXT: [(18)F]MPPF BPND changes in the DRN correlated with changes in right amygdala, which were in turn correlated with changes in hippocampus, insula, subgenual, and orbitofrontal cortex, a circuit implicated in the control of stress, mood, and social behaviors. OXT administration is known to inhibit amygdala activity and results in a decrease of anxiety, whereas high amygdala activity and 5-HT dysregulation have been associated with increased anxiety. The present study reveals a previously unidentified form of interaction between these two systems in the human brain, i.e., the role of OXT in the inhibitory regulation of 5-HT signaling, which could lead to novel therapeutic strategies for mental disorders.
authors.affiliation: Center for Cognitive Neuroscience, Unité Mixte de Recherche 5229, Centre National de la Recherche Scientifique, 69675 Bron, France;University Claude Bernard Lyon 1, 69609 Lyon, France; and.
authors.forename: Raphaelle
authors.initials: R
authors.lastname: Mottolese
authors.affiliation: University Claude Bernard Lyon 1, 69609 Lyon, France; andCentre d'Etude et de Recherche Multimodal et Pluridisciplinaire Imagerie du Vivant, 69003 Lyon, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Redouté
authors.affiliation: Centre d'Etude et de Recherche Multimodal et Pluridisciplinaire Imagerie du Vivant, 69003 Lyon, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Costes
authors.affiliation: University Claude Bernard Lyon 1, 69609 Lyon, France; andCentre d'Etude et de Recherche Multimodal et Pluridisciplinaire Imagerie du Vivant, 69003 Lyon, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Le Bars
authors.affiliation: Center for Cognitive Neuroscience, Unité Mixte de Recherche 5229, Centre National de la Recherche Scientifique, 69675 Bron, France;University Claude Bernard Lyon 1, 69609 Lyon, France; and sirigu@isc.cnrs.fr.
authors.forename: Angela
authors.initials: A
authors.lastname: Sirigu
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D000679:Amygdala / Q000378:metabolism; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D004311:Double-Blind Method; D005625:Frontal Lobe / Q000378:metabolism; D006179:Gyrus Cinguli / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008297:Male; D010121:Oxytocin / Q000008:administration & dosage / Q000494:pharmacology*; D010879:Piperazines / Q000378:metabolism; D049268:Positron-Emission Tomography; D011725:Pyridines / Q000378:metabolism; D011903:Raphe Nuclei / Q000378:metabolism; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D055815:Young Adult
chemical_list: D010879:Piperazines; D011725:Pyridines; D058829:Serotonin 5-HT1 Receptor Antagonists; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D010121:Oxytocin; C416325:4-(2'-methoxyphenyl)-1-(2'-(N-2'-pyridinyl)-p-(18F)fluorobenzamido )ethylpiperazine