Brain–Fluid Barriers: Relevance for Theoretical Controversies Regarding Vasopressin and Oxytocin Memory Research

McEwen, Barbara B.

doi:10.1016/s1054-3589(04)50014-5

Cited by 51 publications

(41 citation statements)

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“…The detailed mechanism of brain penetration of OT and AVP following different methods of administration and the relationship between plasma and central OT and AVP (including possible cross-talks of these neuropeptides at their respective central receptors) is an area that warrants further investigation [111]. In addition to in vitro studies on binding sites in the human brain [106] and recent advances made in identifying neural activity using fMRI [68], the development of specific radioactive labeling of neuropeptides in positron emission tomography will provide a better understanding about how OT and AVP receptors are mapped in the human brain.…”

Section: Methodological Approaches In Human Neuropeptide Researchmentioning

confidence: 99%

Oxytocin, vasopressin, and human social behavior

Heinrichs

Dawans

Domes

2009

Frontiers in Neuroendocrinology

717

481

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Oxytocin, vasopressin, and human social behavior Heinrichs, M;von Dawans, B;von Dawans, B; Domes, G (2009 There is substantial evidence from animal research indicating a key role of the neuropeptides oxytocin (OT) and arginine vasopressin (AVP) in the regulation of complex social cognition and behavior. As social interaction permeates the whole of human society, and the fundamental ability to form attachment is indispensable for social relationships, studies are beginning to dissect the roles of OT and AVP in human social behavior. New experimental paradigms and technologies in human research allow a more nuanced investigation of the molecular basis of social behavior. In addition, a better understanding of the neurobiology and neurogenetics of human social cognition and behavior has important implications for the current development of novel clinical approaches for mental disorders that are associated with social deficits (e.g., autism spectrum disorder, social anxiety disorder, and borderline personality disorder). This review focuses on our recent knowledge of the behavioral, endocrine, genetic, and neural effects of OT and AVP in humans and provides a synthesis of recent advances made in the effort to implicate the oxytocinergic system in the treatment of psychopathological states. t r a c tThere is substantial evidence from animal research indicating a key role of the neuropeptides oxytocin (OT) and arginine vasopressin (AVP) in the regulation of complex social cognition and behavior. As social interaction permeates the whole of human society, and the fundamental ability to form attachment is indispensable for social relationships, studies are beginning to dissect the roles of OT and AVP in human social behavior. New experimental paradigms and technologies in human research allow a more nuanced investigation of the molecular basis of social behavior. In addition, a better understanding of the neurobiology and neurogenetics of human social cognition and behavior has important implications for the current development of novel clinical approaches for mental disorders that are associated with social deficits (e.g., autism spectrum disorder, social anxiety disorder, and borderline personality disorder). This review focuses on our recent knowledge of the behavioral, endocrine, genetic, and neural effects of OT and AVP in humans and provides a synthesis of recent advances made in the effort to implicate the oxytocinergic system in the treatment of psychopathological states.

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Section: Methodological Approaches In Human Neuropeptide Researchmentioning

confidence: 99%

Oxytocin, vasopressin, and human social behavior

Heinrichs

Dawans

Domes

2009

Frontiers in Neuroendocrinology

717

481

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“…This constitutes approximately 0.001% of the administered dose. Oxytocin does not readily cross the blood-brain barrier (McEwen, 2004) and peripheral administration also results in 0.002-0.02% of the dose reaching the brain in rats (Mens et al, 1983; 0.002% in CSF 10 min post-subcutaneous administration of 5 ug; Kang and Park, 2000: 0.02% in brain tissues 60 min post-intravenous administration of 23 ng). Even if such a small proportion accesses the brain, the common dose used in psychiatric studies of 24 IU equivalent to 50 ug should still provide 50 ng reaching the CSF, while baseline endogenous CSF OT concentrations in humans are commonly reported in the range of 15-20 pg/mL (Kagerbauer et al, 2013;Striepens et al, 2013), hence a supra-physiological dose.…”

Section: Intranasal Oxytocin Administrationmentioning

confidence: 99%

“…This is despite the majority of studies reporting no consistent correlation between central and peripheral OT changes (Perlow et al, 1982;Amico et al, 1990;Kendrick et al, 1991;Winslow et al, 2003;Jokinen et al, 2012;Kagerbauer et al, 2013;Striepens et al, 2013). This is attributed to central and peripheral release patterns being governed by separate systems, and the poor ability for OT to cross the blood-brain barrier (McEwen, 2004). In addition, concerns exist with analysis of OT in plasma or serum samples without prior extraction, often against the assay kit manufacturer recommendation, or without proper validation (McCullough et al, 2013;Christensen et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Effects of positive and negative human contacts and intranasal oxytocin on cerebrospinal fluid oxytocin

Rault

2016

Psychoneuroendocrinology

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“…OT is released peripherally primarily from the neurohypophysis by exocytosis (Carson et al, 2013; Viero et al, 2010). Since OT is a relatively large, hydrophilic molecule, blood-brain penetration is 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 released directly in the CNS by OT neurons that project to numerous brain regions from the PVN, separate from those that go to the pituitary (Ross and Young, 2009; Veening et al, 2010).…”

Section: Intranasal Delivery: Mechanismsmentioning

confidence: 99%

Intranasal oxytocin effects on social cognition: A critique

et al. 2014

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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. The use of nasal spray for administering OT in behavioral research has become a standard method, but many questions still exist regarding its action. OT is a peptide that cannot cross the blood-brain barrier, and it has yet to be shown that it does indeed reach the brain when delivered intranasally. Given the evidence, it seems highly likely that OT does affect behavior when delivered as a nasal spray. These effects may be driven by at least three possible mechanisms. First, the intranasally delivered OT may diffuse directly into the CNS where it directly engages OT receptors. Second, the intranasally delivered OT may trigger increased central release via an 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 always “pro-social” and others suggest effects on social 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 social cognition and behavior. We conclude that future work should control carefully for anxiolytic and gender effects, which could underlie inconsistencies in the existing literature.

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Brain–Fluid Barriers: Relevance for Theoretical Controversies Regarding Vasopressin and Oxytocin Memory Research

Cited by 51 publications

References 0 publications

Oxytocin, vasopressin, and human social behavior

Oxytocin, vasopressin, and human social behavior

Effects of positive and negative human contacts and intranasal oxytocin on cerebrospinal fluid oxytocin

Intranasal oxytocin effects on social cognition: A critique

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