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      Neural and Molecular Contributions to Pathological Jealousy and a Potential Therapeutic Role for Intranasal Oxytocin

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          Abstract

          Romantic jealousy, especially in its pathological form, is a significant contributor to both domestic abuse, including partner sexual coercion and even murder, although relatively little research has been conducted on it. Both obsessive and delusional forms have been identified although only the latter is currently recognized as a pathological disorder. Studies in both clinical and healthy populations have identified altered fronto-striatal responsivity as being associated primarily with romantic jealousy and to date drug based treatments have targeted both dopaminergic and serotonergic systems. However, there is increasing interest in a potential role for the neuropeptide oxytocin, which can also modulate dopaminergic and serotonin systems in the brain and has been shown to altered in other psychotic conditions, such as schizophrenia and obsessive compulsive disorder. Recent studies in healthy populations have reported that when oxytocin is administered intranasally it can influence the brain to promote strengthening of romantic bonds and reduce romantic jealousy in both men and women evoked in either imagined or real contexts. These findings indicate a possible therapeutic use of intranasal oxytocin administration in pathological jealousy.

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          Most cited references91

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          Social reward requires coordinated activity of accumbens oxytocin and 5HT

          Social behaviors in species as diverse as honey bees and humans promote group survival but often come at some cost to the individual. Although reinforcement of adaptive social interactions is ostensibly required for the evolutionary persistence of these behaviors, the neural mechanisms by which social reward is encoded by the brain are largely unknown. Here we demonstrate that in mice oxytocin (OT) acts as a social reinforcement signal within the nucleus accumbens (NAc) core, where it elicits a presynaptically expressed long-term depression of excitatory synaptic transmission in medium spiny neurons. Although the NAc receives OT receptor-containing inputs from several brain regions, genetic deletion of these receptors specifically from dorsal raphe nucleus, which provides serotonergic (5-HT) innervation to the NAc, abolishes the reinforcing properties of social interaction. Furthermore, OT-induced synaptic plasticity requires activation of NAc 5-HT1b receptors, the blockade of which prevents social reward. These results demonstrate that the rewarding properties of social interaction in mice require the coordinated activity of OT and 5-HT in the NAc, a mechanistic insight with implications for understanding the pathogenesis of social dysfunction in neuropsychiatric disorders such as autism.
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            Oxytocin modulates neural circuitry for social cognition and fear in humans.

            In non-human mammals, the neuropeptide oxytocin is a key mediator of complex emotional and social behaviors, including attachment, social recognition, and aggression. Oxytocin reduces anxiety and impacts on fear conditioning and extinction. Recently, oxytocin administration in humans was shown to increase trust, suggesting involvement of the amygdala, a central component of the neurocircuitry of fear and social cognition that has been linked to trust and highly expresses oxytocin receptors in many mammals. However, no human data on the effects of this peptide on brain function were available. Here, we show that human amygdala function is strongly modulated by oxytocin. We used functional magnetic resonance imaging to image amygdala activation by fear-inducing visual stimuli in 15 healthy males after double-blind crossover intranasal application of placebo or oxytocin. Compared with placebo, oxytocin potently reduced activation of the amygdala and reduced coupling of the amygdala to brainstem regions implicated in autonomic and behavioral manifestations of fear. Our results indicate a neural mechanism for the effects of oxytocin in social cognition in the human brain and provide a methodology and rationale for exploring therapeutic strategies in disorders in which abnormal amygdala function has been implicated, such as social phobia or autism.
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              Ventromedial prefrontal-subcortical systems and the generation of affective meaning.

              The ventromedial prefrontal cortex (vmPFC) comprises a set of interconnected regions that integrate information from affective sensory and social cues, long-term memory, and representations of the 'self'. Alhough the vmPFC is implicated in a variety of seemingly disparate processes, these processes are organized around a common theme. The vmPFC is not necessary for affective responses per se, but is critical when affective responses are shaped by conceptual information about specific outcomes. The vmPFC thus functions as a hub that links concepts with brainstem systems capable of coordinating organism-wide emotional behavior, a process we describe in terms of the generation of affective meaning, and which could explain the common role played by the vmPFC in a range of experimental paradigms. Copyright © 2012 Elsevier Ltd. All rights reserved.

                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                20 April 2021
                2021
                : 12
                : 652473
                Affiliations
                The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China
                Author notes

                Edited by: Ana Fortuna, University of Coimbra, Portugal

                Reviewed by: Luigia Trabace, University of Foggia, Italy

                Christopher Stuart Walker, The University of Auckland, New Zealand

                *Correspondence: Keith M. Kendrick, k.kendrick.uestc@ 123456gmail.com

                This article was submitted to Translational Pharmacology, a section of the journal Frontiers in Pharmacology

                Article
                652473
                10.3389/fphar.2021.652473
                8094533
                33959017
                cf053070-9f97-4439-9d43-bf647df88c40
                Copyright © 2021 Zheng and Kendrick.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 12 January 2021
                : 31 March 2021
                Funding
                Funded by: National Natural Science Foundation of China-Guangdong Joint Fund 10.13039/501100014857
                Award ID: Unassigned
                Funded by: Guangdong Provincial Key Laboratory of Research in Structural Birth Defect disease 10.13039/100017340
                Award ID: Unassigned
                Categories
                Pharmacology
                Mini Review

                Pharmacology & Pharmaceutical medicine
                pathological jealousy,intranasal oxytocin,partner bonds,social reward,dopamine,serotonin

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