Localization of oxytocin binding sites in the human brainstem and upper spinal cord: an autoradiographic study.
ABSTRACT Two different ligands, tritiated oxytocin and a newly synthesized and monoiodinated oxytocin antagonist, were used to reveal sites which bind oxytocin in the brainstem and upper spinal cord of 12 human subjects. Tissue sections were incubated with either ligand at a concentration close to their respective dissociation constants determined in human uterus and rat brain. Specificity of binding was assessed in presence of unlabelled oxytocin in excess. Comparable results were obtained using tritiated or iodinated ligand. Labelling was most intense in the substantia nigra pars compacta, the substantiae gelatinosae of the caudal spinal trigeminal nucleus and of the dorsal horn of the upper spinal cord, as well as in the medio-dorsal region of the nucleus of the solitary tract. Binding was also detected in the rest of the nucleus of the solitary tract and in other areas, including the oral and interpolar parts of the spinal trigeminal nucleus, the hypoglossal nucleus and the area postrema. Presence of oxytocin binding sites in regions concerned with sensory, autonomic and motor processing suggests that oxytocin could act as a neurotransmitter or neuromodulator in the human central nervous system.
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ABSTRACT: Oxytocin (OXT) plays a prominent role in social cognition and may have clinical applications for disorders such as autism, schizophrenia and social anxiety. The neural basis of its mechanism of action remains unclear. We conducted a systematic literature review of placebo-controlled imaging studies using OXT as a pharmacological manipulator of brain activity. We identified a total of 21 studies for inclusion in our review, and after applying additional selection criteria, 11 of them were included in our fMRI voxel-based meta-analysis. The results demonstrate consistent alterations in activation of brain regions, including the temporal lobes and insula, during the processing of social stimuli, with some variation dependent on sex and task. The meta-analysis revealed significant left insular hyperactivation after OXT administration, suggesting a potential modulation of neural circuits underlying emotional processing. This quantitative review included only a limited number of studies, thus the conclusions of our analysis should be interpreted cautiously. This limited sample size precluded a more detailed exploration of potential confounding factors, such as sex or other demographic factors, that may have affected our meta-analysis. Oxytocin has a wide range of effects over neural activity in response to social and emotional processing, which is further modulated by sex and task specificity. The magnitude of this neural activation is largest in the temporal lobes, and a meta-analysis across all tasks and both sexes showed that the left insula demonstrated the most robust activation to OXT administration.Journal of psychiatry & neuroscience: JPN 01/2015; 40(1):E1-E22. · 7.49 Impact Factor
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ABSTRACT: The neuropeptide oxytocin was first noted for its capacity to promote uterine contractions and facilitate delivery in mammals. The study of oxytocin has grown to include awareness that this peptide is a neuromodulator with broad effects throughout the body. Accumulating evidence suggests that oxytocin is a powerful signal to the fetus, helping to prepare the offspring for the extrauterine environment. Concurrently, the use of exogenous oxytocin or other drugs to manipulate labor has become common practice. The use of oxytocin to expedite labor and minimize blood loss improves both infant and maternal survival under some conditions. However, further investigation is needed to assess the developmental consequences of changes in oxytocin, such as those associated with pre-eclampsia or obstetric manipulations associated with birth. This review focuses on the role of endogenous and exogenous oxytocin as a neurochemical signal to the fetal nervous system. We also examine the possible developmental consequences, including those associated with autism spectrum disorder, that arise from exogenous oxytocin supplementation during labor.This article is protected by copyright. All rights reserved.Journal of Neuroendocrinology 07/2014; · 3.51 Impact Factor
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ABSTRACT: Background Animal and human studies highlight the role of oxytocin in social cognition and behaviour and the potential of intranasal oxytocin (IN-OT) to treat social impairment in neuropsychiatric disorders such as autism. However, extensive efforts to evaluate its central actions and therapeutic efficacy may be marred by the absence of data regarding its temporal dynamics and sites of action in the living human brain. Methods In a placebo-controlled study, we used arterial spin labeling to measure IN-OT induced changes in resting regional cerebral blood flow (rCBF) in 32 healthy men. Volunteers were blinded regarding the nature of the compound they received. rCBF data were acquired 15min before and up to 78min following treatment onset (40IU of IN-OT or placebo). The data were analysed using mass-univariate and multivariate PR techniques. Results We obtained robust evidence delineating an oxytocinergic network comprising regions expected to express oxytocin receptors, based on histological evidence, and including core regions of the brain circuitry underpinning social cognition and emotion processing. PR on rCBF maps indicated that IN-OT induced changes were sustained over the entire post-treatment observation interval (25-78min) and consistent with a pharmacodynamic profile showing a peak response at 39-51min. Conclusions Our study provides the first visualisation and quantification of IN-OT induced changes in rCBF in the living human brain unaffected by cognitive, affective, or social manipulations. Our findings can inform theoretical and mechanistic models regarding IN-OT effects on typical and atypical social behaviour and guide future experiments (e.g. regarding the timing of experimental manipulations).Biological Psychiatry 10/2014; · 9.47 Impact Factor