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: Raphaelle Mottolese, Jérôme Redouté, Nicolas Costes, Didier Le Bars, Angela Sirigu
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 111 Issue 23 Pg. 8637-42 (Jun 10 2014) ISSN: 1091-6490 [Electronic] United States
• PMID: 24912179 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Piperazines
• Pyridines
• Serotonin 5-HT1 Receptor Antagonists
• Receptor, Serotonin, 5-HT1A
• Serotonin
• Oxytocin
• 4-(2'-methoxyphenyl)-1-(2'-(N-2'-pyridinyl)-p-(18F)fluorobenzamido )ethylpiperazine

Topics

• Administration, Intranasal
• Adult
• Amygdala (metabolism)
• Binding, Competitive (drug effects)
• Brain (metabolism)
• Double-Blind Method
• Frontal Lobe (metabolism)
• Gyrus Cinguli (metabolism)
• Hippocampus (metabolism)
• Humans
• Male
• Oxytocin (administration & dosage, pharmacology)
• Piperazines (metabolism)
• Positron-Emission Tomography
• Pyridines (metabolism)
• Raphe Nuclei (metabolism)
• Receptor, Serotonin, 5-HT1A (metabolism)
• Serotonin (metabolism)
• Serotonin 5-HT1 Receptor Antagonists (administration & dosage, pharmacology)
• Signal Transduction (drug effects)
• Young Adult