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      Intranasal administration of oxytocin: Behavioral and clinical effects, a review

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          Highlights

          • The mechanisms behind the effects of IN-applied substances need more attention.

          • The mechanisms involved in the brain-distribution of IN-OT are completely unexplored.

          • The possibly cascading effects of IN-OT on the intrinsic OT-system require serious investigation.

          • IN-OT induces clear and specific changes in neural activation.

          • IN-OT is a promising approach to treat certain clinical symptoms.

          Abstract

          The intranasal (IN-) administration of substances is attracting attention from scientists as well as pharmaceutical companies. The effects are surprisingly fast and specific. The present review explores our current knowledge about the routes of access to the cranial cavity. ‘Direct-access-pathways’ from the nasal cavity have been described but many additional experiments are needed to answer a variety of open questions regarding anatomy and physiology.

          Among the IN-applied substances oxytocin (OT) has an extensive history. Originally applied in women for its physiological effects related to lactation and parturition, over the last decade most studies focused on their behavioral ‘prosocial’ effects: from social relations and ‘trust’ to treatment of ‘autism’.

          Only very recently in a microdialysis study in rats and mice, the ‘direct-nose-brain-pathways’ of IN-OT have been investigated directly, implying that we are strongly dependent on results obtained from other IN-applied substances. Especially the possibility that IN-OT activates the ‘intrinsic’ OT-system in the hypothalamus as well needs further clarification.

          We conclude that IN-OT administration may be a promising approach to influence human communication but that the existing lack of information about the neural and physiological mechanisms involved is a serious problem for the proper understanding and interpretation of the observed effects.

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          Most cited references425

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          Oxytocin, vasopressin, and the neurogenetics of sociality.

          There is growing evidence that the neuropeptides oxytocin and vasopressin modulate complex social behavior and social cognition. These ancient neuropeptides display a marked conservation in gene structure and expression, yet diversity in the genetic regulation of their receptors seems to underlie natural variation in social behavior, both between and within species. Human studies are beginning to explore the roles of these neuropeptides in social cognition and behavior and suggest that variation in the genes encoding their receptors may contribute to variation in human social behavior by altering brain function. Understanding the neurobiology and neurogenetics of social cognition and behavior has important implications, both clinically and for society.
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            The functional role of the parieto-frontal mirror circuit: interpretations and misinterpretations.

            The parieto-frontal cortical circuit that is active during action observation is the circuit with mirror properties that has been most extensively studied. Yet, there remains controversy on its role in social cognition and its contribution to understanding the actions and intentions of other individuals. Recent studies in monkeys and humans have shed light on what the parieto-frontal cortical circuit encodes and its possible functional relevance for cognition. We conclude that, although there are several mechanisms through which one can understand the behaviour of other individuals, the parieto-frontal mechanism is the only one that allows an individual to understand the action of others 'from the inside' and gives the observer a first-person grasp of the motor goals and intentions of other individuals.
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              Dopamine reward circuitry: two projection systems from the ventral midbrain to the nucleus accumbens-olfactory tubercle complex.

              Anatomical and functional refinements of the meso-limbic dopamine system of the rat are discussed. Present experiments suggest that dopaminergic neurons localized in the posteromedial ventral tegmental area (VTA) and central linear nucleus raphe selectively project to the ventromedial striatum (medial olfactory tubercle and medial nucleus accumbens shell), whereas the anteromedial VTA has few if any projections to the ventral striatum, and the lateral VTA largely projects to the ventrolateral striatum (accumbens core, lateral shell and lateral tubercle). These findings complement the recent behavioral findings that cocaine and amphetamine are more rewarding when administered into the ventromedial striatum than into the ventrolateral striatum. Drugs such as nicotine and opiates are more rewarding when administered into the posterior VTA or the central linear nucleus than into the anterior VTA. A review of the literature suggests that (1) the midbrain has corresponding zones for the accumbens core and medial shell; (2) the striatal portion of the olfactory tubercle is a ventral extension of the nucleus accumbens shell; and (3) a model of two dopamine projection systems from the ventral midbrain to the ventral striatum is useful for understanding reward function. The medial projection system is important in the regulation of arousal characterized by affect and drive and plays a different role in goal-directed learning than the lateral projection system, as described in the variation-selection hypothesis of striatal functional organization.
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                Author and article information

                Contributors
                Journal
                Neurosci Biobehav Rev
                Neurosci Biobehav Rev
                Neuroscience and Biobehavioral Reviews
                Elsevier Ltd.
                0149-7634
                1873-7528
                4 May 2013
                September 2013
                4 May 2013
                : 37
                : 8
                : 1445-1465
                Affiliations
                [a ]Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, P.O. Box 80082, 3508 TB, Utrecht, The Netherlands
                [b ]Department of Anatomy (109), Radboud University of Medical Sciences, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands
                Author notes
                [* ]Corresponding author at: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, P.O. Box 80082, 3508 TB, Utrecht, the Netherlands. Tel.: +31 243614298. j.veening@ 123456anat.umcn.nl
                Article
                S0149-7634(13)00108-5
                10.1016/j.neubiorev.2013.04.012
                7112651
                23648680
                1b44c987-526e-4409-84dc-e0d72a3ae2a6
                Copyright © 2013 Elsevier Ltd. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 1 November 2012
                : 22 April 2013
                : 24 April 2013
                Categories
                Article

                Neurosciences
                intranasal administration,oxytocin,behavioral effects,clinical effects
                Neurosciences
                intranasal administration, oxytocin, behavioral effects, clinical effects

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