Oxytocin-messages via the cerebrospinal fluid: Behavioral effects; a review

Veening, Jan G.; Jong, Trynke de; Barendregt, Henk

doi:10.1016/j.physbeh.2010.05.004

Cited by 114 publications

(107 citation statements)

References 344 publications

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“…Thus, startle appears to be as sensitive behavioral measure as passive avoidance for peripherally administered oxytocin, but does not answer the question of whether the site(s) of action are peripheral or central. Peripheral and central oxytocin systems are regulated differently, release very different amounts of oxytocin, and metabolize oxytocin at different rates, suggesting that the two systems are largely independent (Veening et al, 2010). We have preliminary data that oxytocin infused into the lateral ventricle in the same range of doses we administered subcutaneously might not reduce fear-potentiated startle or background anxiety (Ayers et al, 2010).…”

Section: Discussionmentioning

confidence: 76%

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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Section: Discussionmentioning

confidence: 76%

Oxytocin Reduces Background Anxiety in a Fear-Potentiated Startle Paradigm

Missig

Ayers

Schulkin

et al. 2010

Neuropsychopharmacol

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“…Peripherally administered oxytocin has been shown to increase neural activity as measured by neuronal Fos expression in oxytocin-producing neurons of the supraoptic and paraventricular hypothalamic nuclei, and areas known to be important for anxiety, such as the central nucleus of the amygdala, locus coeruleus, and parabrachial nucleus (Carson et al, 2010) that contain oxytocin receptors (Tribollet et al, 1992). Oxytocin-synthesizing neurons in the paraventricular hypothalamic and supraoptic nuclei have extensive networks of dendrites and axons, which penetrate into the ventricles and subarachnoid space to release oxytocin (Veening et al, 2010). Oxytocin receptors in many brain areas are potentially activated by oxytocin released or injected into the CSF, including the paraventricular hypothalamic nucleus (Gimpl and Fahrenholz, 2001;Veening et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Oxytocin-synthesizing neurons in the paraventricular hypothalamic and supraoptic nuclei have extensive networks of dendrites and axons, which penetrate into the ventricles and subarachnoid space to release oxytocin (Veening et al, 2010). Oxytocin receptors in many brain areas are potentially activated by oxytocin released or injected into the CSF, including the paraventricular hypothalamic nucleus (Gimpl and Fahrenholz, 2001;Veening et al, 2010). Whereas these oxytocin receptive areas along the ventricles and subarachnoid space may mediate many behaviors, including grooming, following ICV administration of oxytocin (Stivers et al, 1988;Van Erp et al, 1993b;Veening et al, 2010), background anxiety does not appear to be one of these.…”

Section: Discussionmentioning

confidence: 99%

Oxytocin Reduces Background Anxiety in a Fear-Potentiated Startle Paradigm: Peripheral vs Central Administration

Ayers

Missig

Schulkin

et al. 2011

Neuropsychopharmacol

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Oxytocin is known to have anti-anxiety and anti-stress effects. Using a fear-potentiated startle paradigm in rats, we previously demonstrated that subcutaneously administered oxytocin suppressed acoustic startle following fear conditioning compared with startle before fear conditioning (termed background anxiety), but did not have an effect on cue-specific fear-potentiated startle. The findings suggest oxytocin reduces background anxiety, an anxious state not directly related to cue-specific fear, but sustained beyond the immediate threat. The goal of the present study was to compare the effects of centrally and peripherally administered oxytocin on background anxiety and cue-specific fear. Male rats were given oxytocin either subcutaneously (SC) or intracerebroventricularly (ICV) into the lateral ventricles before fear-potentiated startle testing. Oxytocin doses of 0.01 and 0.1 mg/kg SC reduced background anxiety. ICV administration of oxytocin at doses from 0.002 to 20 mg oxytocin had no effect on background anxiety or cue-specific fearpotentiated startle. The 20 mg ICV dose of oxytocin did reduce acoustic startle in non-fear conditioned rats. These studies indicate that oxytocin is potent and effective in reducing background anxiety when delivered peripherally, but not when delivered into the cerebroventricular system. Oxytocin given systemically may have anti-anxiety properties that are particularly germane to the hypervigilance and exaggerated startle typically seen in many anxiety and mental health disorder patients.

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“…In this way, it has been shown that the administration method can crucially influence the OT penetration of blood-brain barrier. In this way, many studies showed significant cerebrospinal fluid OT levels after intranasal administration both in humans (Striepens et al 2013) and rats (as reviewed by Veening et al 2010), but also in macaques (Dal Monte et al 2014). By contrast, animal-based studies showed that less than 0.1% of the administered OT can cross the blood-brain barrier by intravenous mean (Kendrick et al 1991).…”

Section: Introductionmentioning

confidence: 99%

Preliminary Data on Some Behavioral Changes Induced by Short-Term Intraperitoneal Oxytocin Administration in Aged Rats

et al. 2018

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Results: Increased mobility and decreased anxiety behaviors were reported for the aged intraperitoneal OT-treated animals, as compared with controls, during FST and OFT, and respectively FST, EPM, and OFT. Also, decreased depressive-like behaviors were observed in the same animal group during FST and ST. Moreover, a decrease in anxiolytic behavior was observed as exposed to stressful stimuli (such as grooming behavior in OFT, and forced grooming behavior in ST), and as exposed to social stimuli (such as grooming behavior in TCT

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Oxytocin-messages via the cerebrospinal fluid: Behavioral effects; a review

Cited by 114 publications

References 344 publications

Oxytocin Reduces Background Anxiety in a Fear-Potentiated Startle Paradigm

Oxytocin Reduces Background Anxiety in a Fear-Potentiated Startle Paradigm

Oxytocin Reduces Background Anxiety in a Fear-Potentiated Startle Paradigm: Peripheral vs Central Administration

Preliminary Data on Some Behavioral Changes Induced by Short-Term Intraperitoneal Oxytocin Administration in Aged Rats

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