The last decade has seen a large number of published findings supporting the hypothesis that intranasally delivered oxytocin (OT) can enhance the processing of social stimuli and regulate social emotion-related behaviors such as trust memory fidelity and anxiety. indirect peripheral mechanism. And third the indirect peripheral effects may directly lead to behavioral effects via some mechanism other than increased central release. Although intranasally delivered OT likely affects behavior there are conflicting reports as to the exact nature of those behavioral changes: some studies suggest that OT effects are not usually “pro-social” as well as others suggest effects on interpersonal behaviors are due to a more general anxiolytic effect. In this critique we draw from work in healthy human populations and the animal literature to review the mechanistic aspects of intranasal OT delivery and to discuss intranasal OT effects on interpersonal cognition and behavior. We conclude that future work should control carefully for anxiolytic and gender effects which could underlie inconsistencies SL-327 in the existing literature. Keywords: Oxytocin Intranasal administration CSF Social Stimuli pro-social neuropeptide stress Social Cognition Introduction Oxytocin (OT) is usually a peptide that has numerous functions in the body both peripherally as a hormone and centrally as a neurotransmitter and OT-like peptides can be found in nearly all vertebrate species (Gimple and Farenholtz 2001 Peripheral functions are wide ranging. OT has a well-established role in reproductive function (Corona et al. 2012 Courtois et al. 2013 and in parturition and lactation in females (Carson et al. 2013 Gimple and Farenholtz 2001 Synthetic OT has been used to assist in childbirth for decades. In addition OT receptors are located in visceral organs such as kidneys and pancreas as well as in the heart excess fat cells and adrenal glands (Gimple and Farenholtz 2001 and OT has been found to be SL-327 involved in the regulation of water balance bone density and appetite (Carson et al. 2013 In contrast it has been suggested that OT effects in the central nervous system (CNS) might be more specific with OT playing an important role in SL-327 modulating interpersonal behaviors and the processing of interpersonal stimuli. Whether these behavioral changes are modulated by OT in system-specific ways or due to more general effects are however unknown. The study of central effects of OT has been carried out in animal models and humans using different delivery methods: in animals both SL-327 central and peripheral administration has been used while in humans studies investigating the effects of exogenous OT typically use intranasal spray for delivery with few exceptions (Hollander et al. 2003 How or if the OT enters the brain using this method is usually however still unknown. The purpose of this critique is usually twofold. We firstly discuss the potential mechanisms by which OT could enter the brain and weigh the evidence from work in animals. Implications for human studies using intranasal OT are discussed. We then provide an overview of intranasal OT effects on interpersonal cognition in healthy humans and explore whether OT is usually truly a neuropeptide with specifically “pro-social” effects. We incorporate findings published since other recent reviews on this topic (Bartz et al. 2011 Guastella et al. 2013 MacDonald et al. 2011 identify potential confounds that could underlie current inconsistencies in the literature and provide suggestions as to how these could be resolved. In tying together both the mechanistic and behavioral aspects of intranasal OT delivery we provide a summary several issues as a guide for future research. Intranasal delivery: mechanisms The OT peptide is usually comprised of nine amino acids and is produced in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus in mammals. OT is usually SL-327 released peripherally primarily Rabbit polyclonal to LPGAT1. from the neurohypophysis by exocytosis SL-327 (Carson et al. 2013 Viero et al. 2010 Since OT is usually a relatively large hydrophilic molecule blood-brain penetration is usually too poor to cause any measurable effects on central systems (McEwen 2004 so peripheral OT likely re-enters the brain in negligible amounts. Instead OT is usually released directly in the CNS by OT neurons that project to numerous brain regions from the PVN individual from those that go to the pituitary (Ross and Young 2009 Veening et al. 2010 OT receptors are widely distributed through many brain areas in rat including the spinal cord brainstem hypothalamus amygdala and nucleus accumbens (Ross and Young 2009 While localization of OT receptors have yet to be definitively mapped in primates and humans (Toloczko et al. 1997 efforts are being made to develop a radioligand that will bind with.