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

Jan G Veening, Berend Olivier, Jan G Veening, Berend Olivier

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.

Keywords: Behavioral effects; Clinical effects; Intranasal administration; Oxytocin.

Copyright © 2013 Elsevier Ltd. All rights reserved.

Figures

Fig. 1
Fig. 1
The figure shows a midsagittal section of the rat brain (kindly provided by Prof. L.W.Swanson), with the fiber bundles, crossing the midline, indicated in black. The orange arrows indicate the flow of oxytocin (OT) from the natural hypothalamic sources: the paraventricular hypothalamic nucleus (PVN) and the supraoptic nucleus (SON). After (dendritic) release OT follows the flow of the cerebrospinal fluid (CSF) through the ventricular system and along the external surface of the brain. Eventually, more than 50% of the ‘central’ OT is leaving the cranial cavity along the olfactory fibers, through the cribriform plate into the nose lymphatics. The blue arrows suggest the entrance of intranasally applied OT (in-OT), entering the cranial cavity and the CSF along the olfactory fibers but possibly also by following the trigeminal nerve. The scheme is based on assumptions obtained from other neuropeptide studies (like Thorne et al., 2004), since the entrance and distribution of in-OT itself has never been studied, yet. The arrows suggest a rostral to caudal distribution through the brain and CSF from the rostral entrance, supported by the OT entering the brainstem along the trigeminal fibers (but this entrance remains to be shown to be relevant for OT!). The more strongly ‘inundated’ parts of the brain appear to be the ventral parts and include the hypothalamus and amygdaloid regions. For further details, see text, and Veening et al. (2010) and Veening and Barendregt (2010). The numbers 1–5 indicate OT-receptive brain areas, containing OT-receptors.

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