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      Oxytocin and Eating Disorders: A Narrative Review on Emerging Findings and Perspectives

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          Abstract

          Background:

          The hypothalamic neuropeptide oxytocin regulates reproductive behavior and mother-infant interaction, and conclusive studies in humans indicate that oxytocin is also a potent modulator of psychosocial function. Pilot experiments have yielded first evidence that this neuropeptide moreover influences eating behavior.

          Methods:

          We briefly summarize currently available studies on the involvement of the oxytocin system in the pathophysiology of eating disorders, as well as on the effects of oxytocin administration in patients with these disorders.

          Results:

          Brain administration of oxytocin in animals with normal weight, but also with diet-induced or genetically induced obesity, attenuates food intake and reduces body weight. In normal-weight and obese individuals, acute intranasal oxytocin delivery curbs calorie intake from main dishes and snacks. Such effects might converge with the poignant social and cognitive impact of oxytocin to also improve dysfunctional eating behavior in the therapeutic context. This assumption has received support in first studies showing that oxytocin might play a role in the disease process of anorexia nervosa. In contrast, respective experiments in patients with bulimia nervosa and binge eating disorder are still scarce.

          Conclusions:

          We propose a framework of oxytocin’s role and its therapeutic potential in eating disorders that aims at integrating social and metabolic aspects of its pharmacological profile, and ponder perspectives and limitations of oxytocin use in the clinical setting.

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          Most cited references87

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          Neurobiology of food intake in health and disease.

          Under normal conditions, food intake and energy expenditure are balanced by a homeostatic system that maintains stability of body fat content over time. However, this homeostatic system can be overridden by the activation of 'emergency response circuits' that mediate feeding responses to emergent or stressful stimuli. Inhibition of these circuits is therefore permissive for normal energy homeostasis to occur, and their chronic activation can cause profound, even life-threatening, changes in body fat mass. This Review highlights how the interplay between homeostatic and emergency feeding circuits influences the biologically defended level of body weight under physiological and pathophysiological conditions.
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            Delivery of insulin-like growth factor-I to the rat brain and spinal cord along olfactory and trigeminal pathways following intranasal administration.

            We investigated the CNS delivery of insulin-like growth factor-I (IGF-I), a 7.65 kDa protein neurotrophic factor, following intranasal administration and the possible pathways and mechanisms underlying transport from the nasal passages to the CNS. Anesthetized adult male Sprague-Dawley rats were given [125I]-IGF-I intranasally or intravenously and then killed by perfusion-fixation within 30 min. Other animals were killed following cisternal puncture and withdrawal of cerebrospinal fluid (CSF) or intranasal administration of unlabeled IGF-I or vehicle. Both gamma counting of microdissected tissue and high resolution phosphor imaging of tissue sections showed that the tissue concentrations and distribution following intranasal administration were consistent with two routes of rapid entry into the CNS: one associated with the peripheral olfactory system connecting the nasal passages with the olfactory bulbs and rostral brain regions (e.g. anterior olfactory nucleus and frontal cortex) and the other associated with the peripheral trigeminal system connecting the nasal passages with brainstem and spinal cord regions. Intranasal administration of [125I]-IGF-I also targeted the deep cervical lymph nodes, consistent with their possible role in lymphatic drainage of both the nasal passages and the CNS. Cisternal CSF did not contain [125I]-IGF-I following intranasal administration. Intravenous [125I]-IGF-I resulted in blood and peripheral tissue exposure similar to that seen following intranasal administration but CNS concentrations were significantly lower. Finally, delivery of IGF-I into the CNS activated IGF-I signaling pathways, confirming some portion of the IGF-I that reached CNS target sites was functionally intact. The results suggest intranasally delivered IGF-I can bypass the blood-brain barrier via olfactory- and trigeminal-associated extracellular pathways to rapidly elicit biological effects at multiple sites within the brain and spinal cord.
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              Elevated cerebrospinal fluid and blood concentrations of oxytocin following its intranasal administration in humans

              There has been an unprecedented interest in the modulatory effects of intranasal oxytocin on human social cognition and behaviour, however as yet no study has actually demonstrated that this modality of administration increases concentrations of the peptide in the brain as well as blood in humans. Here using combined blood and cerebrospinal fluid (CSF) sampling in subjects receiving either 24 IU of oxytocin (n = 11) or placebo (n = 4) we have shown that oxytocin levels significantly increased in both plasma and CSF. However, whereas oxytocin plasma concentrations peaked at 15 min after intranasal administration and decreased after 75 min, CSF concentrations took up to 75 min to reach a significant level. Moreover, there was no correlation (r = <0.10) between oxytocin plasma and CSF concentrations. Together, these data provide crucial insights into the plasma and CSF kinetics of intranasally administered oxytocin.
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                Author and article information

                Journal
                Curr Neuropharmacol
                Curr Neuropharmacol
                CN
                Current Neuropharmacology
                Bentham Science Publishers
                1570-159X
                1875-6190
                October 2018
                October 2018
                : 16
                : 8
                : 1111-1121
                Affiliations
                University Hospital Tübingen, Department of Psychosomatic Medicine and Psychotherapy , Tübingen, , Germany;
 Institute of Medical Psychology and Behavioral Neurobiology, University of Tübingen , Tübingen, , Germany; German Center for Diabetes Research (DZD), Tübingen, , Germany; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, , Germany
                Author notes
                [* ]Address correspondence to this author at the Department of Medical 
Psychology and Behavioral Neurobiology, Faculty of Medicine, University of Tuebingen, 72076 Tuebingen, Germany; Tel/Fax: ++49-7071-29-88925, +49-7071-29-25016; E-mail: manfred.hallschmid@ 123456uni-tuebingen.de
                Article
                CN-16-1111
                10.2174/1570159X15666171128143158
                6187754
                29189166
                dd2cb740-7839-4916-b6d1-8f1298182623
                © 2018 Bentham Science Publishers

                This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) ( https://creativecommons.org/licenses/by-nc/4.0/legalcode), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

                History
                : 14 June 2017
                : 27 August 2017
                : 23 November 2017
                Categories
                Article

                Pharmacology & Pharmaceutical medicine
                anorexia nervosa,binge eating disorder,bulimia nervosa,eating behavior,eating disorders,oxytocin,therapeutic options

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