The Role of Oxytocin in Neuropsychiatric Disorders

Marazziti, Donatella; Dell’Osso, Mario Catena

doi:10.2174/092986708783885291

Cited by 81 publications

(28 citation statements)

References 122 publications

(133 reference statements)

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“…The serotonin system has been implicated in the neuropathology of depression, and current antidepressant drugs block the serotonin transporter, resulting in increased extracellular serotonin (Kent, 2000). There is some evidence of altered oxytocin systems in depression (Marazziti and Catena Dell'osso, 2008). Thus, we would predict that enhancing central OXTR neurotransmission would not only decrease anxiety, but may also have antidepressant effects through stimulating serotonin neurotransmission.…”

Section: Discussionmentioning

confidence: 99%

Evidence That Oxytocin Exerts Anxiolytic Effects via Oxytocin Receptor Expressed in Serotonergic Neurons in Mice

Yoshida¹,

Takayanagi²,

Inoue³

et al. 2009

J. Neurosci.

512

493

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The oxytocin receptor has been implicated in the regulation of reproductive physiology as well as social and emotional behaviors. The neurochemical mechanisms by which oxytocin receptor modulates social and emotional behavior remains elusive, in part because of a lack of sensitive and selective antibodies for cellular localization. To more precisely characterize oxytocin receptor-expressing neurons within the brain, we generated an oxytocin receptor-reporter mouse in which part of the oxytocin receptor gene was replaced with Venus cDNA (a variant of yellow fluorescent protein). Examination of the Venus expression revealed that, in the raphe nuclei, about one-half of tryptophan hydroxylase-immunoreactive neurons were positive for Venus, suggesting a potential role for oxytocin in the modulation of serotonin release. Oxytocin infusion facilitated serotonin release within the median raphe nucleus and reduced anxiety-related behavior. Infusion of a 5-HT 2A/2C receptor antagonist blocked the anxiolytic effect of oxytocin, suggesting that oxytocin receptor activation in serotonergic neurons mediates the anxiolytic effects of oxytocin. This is the first demonstration that oxytocin may regulate serotonin release and exert anxiolytic effects via direct activation of oxytocin receptor expressed in serotonergic neurons of the raphe nuclei. These results also have important implications for psychiatric disorders such as autism and depression in which both the oxytocin and serotonin systems have been implicated.

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Section: Discussionmentioning

confidence: 99%

Evidence That Oxytocin Exerts Anxiolytic Effects via Oxytocin Receptor Expressed in Serotonergic Neurons in Mice

Yoshida¹,

Takayanagi²,

Inoue³

et al. 2009

J. Neurosci.

512

493

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“…As OT has been shown to reduce social anxiety and increase social abilities in animal and human studies, the neuropeptide might be a significant target for novel therapeutic approaches in several mental disorders that are characterized by social interaction pathology [68,109]. As for the anxiogenic and aggression-related role of AVP, the development of selective V1a and V1b receptor antagonists, as known from animal studies [49,58], is a promising target for human neuropsychopharmacological research, in particular in the treatment of stress-related disorders and disorders with interpersonal violence such as antisocial personality disorder [35].…”

Section: Discussionmentioning

confidence: 99%

Oxytocin, vasopressin, and human social behavior

Heinrichs

Dawans

Domes

2009

Frontiers in Neuroendocrinology

706

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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“…Oxytocin has recently received considerable attention for its role in social behavior, and as a possible target for a number of psychiatric disorders, particularly, anxiety, post-partum depression, and autism (Carter, 2007;Heinrichs et al, 2009;Macdonald and Macdonald, 2010;Marazziti and Catena Dell'osso, 2008;Neumann, 2008). Oxytocin is a nonapeptide released in blood from the hypothalamo-neurohypophysial system and other peripheral organs, and in the brain within the hypothalamus, amygdala, bed nucleus of the stria terminals, brainstem, and other regions from neurons originating in the hypothalamic paraventricular and supraoptic nuclei (Gimpl and Fahrenholz, 2001;Kiss and Mikkelsen, 2005).…”

Section: Introductionmentioning

confidence: 99%

Oxytocin Reduces Background Anxiety in a Fear-Potentiated Startle Paradigm

Missig

Ayers

Schulkin

et al. 2010

Neuropsychopharmacol

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Oxytocin reportedly decreases anxious feelings in humans and may therefore have therapeutic value for anxiety disorders, such as post-traumatic stress disorder (PTSD). As PTSD patients have exaggerated startle responses, a fear-potentiated startle paradigm in rats may have face validity as an animal model to examine the efficacy of oxytocin in treating these symptoms. Oxytocin (0, 0.01, 0.1, or 1.0 mg, subcutaneously) was given either 30 min before fear conditioning, immediately after fear conditioning, or 30 min before fear-potentiated startle testing to assess its effects on acquisition, consolidation, and expression of conditioned fear, respectively. Startle both in the presence and absence of the fear-conditioned light was significantly diminished by oxytocin when administered at acquisition, consolidation, or expression. There was no specific effect of oxytocin on light fear-potentiated startle. In an additional experiment, oxytocin had no effects on acoustic startle without previous fear conditioning. Further, in a context-conditioned test, previous light-shock fear conditioning did not increase acoustic startle during testing when the fear-conditioned light was not presented. The data suggest that oxytocin did not diminish cue-specific conditioned nor contextually conditioned fear, but reduced background anxiety. This suggests that oxytocin has unique effects of decreasing background anxiety without affecting learning and memory of a specific traumatic event. Oxytocin may have antianxiety properties that are particularly germane to the hypervigilance and exaggerated startle typically seen in PTSD patients.

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The Role of Oxytocin in Neuropsychiatric Disorders

Cited by 81 publications

References 122 publications

Evidence That Oxytocin Exerts Anxiolytic Effects via Oxytocin Receptor Expressed in Serotonergic Neurons in Mice

Evidence That Oxytocin Exerts Anxiolytic Effects via Oxytocin Receptor Expressed in Serotonergic Neurons in Mice

Oxytocin, vasopressin, and human social behavior

Oxytocin Reduces Background Anxiety in a Fear-Potentiated Startle Paradigm

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