Oxytocin as a natural antipsychotic: a study using oxytocin knockout mice

Caldwell, Heather K.; Stephens, Shelly L.; Young, W. Scott

doi:10.1038/sj.mp.4002150

Cited by 97 publications

(78 citation statements)

References 81 publications

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“…It is possible that reduction in PPI at the luteal phase is not fully explained by changes in estrogen and also includes the influence of hormones, such as oxytocin. Oxytocin varies across the menstrual cycle in non-pill user healthy young women (lower during the luteal phase compared with the follicular and ovulatory phases; eg, Salonia et al, 2005), and shown recently to have influence in PPI, via glutamatergic component, in experimental animals (Caldwell et al, 2009). This study may also be limited by relatively smaller fluctuations in estrogen, relative to progesterone.…”

Section: Ovarian Hormones and Human Sensorimotor Gating V Kumari Et Almentioning

confidence: 99%

Evidence for a Role of Progesterone in Menstrual Cycle-Related Variability in Prepulse Inhibition in Healthy Young Women

Kumari

Konstantinou

Papadopoulos

et al. 2009

Neuropsychopharmacol

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Prepulse inhibition (PPI) of the startle response is sensitive to sex, with healthy young women showing less PPI compared with age-matched men, and varies according to the menstrual cycle phase in women. Relatively less is known regarding sex and hormonal influences in prepulse facilitation (PPF). Menstrual phase-related variability in PPI is suggested to be mediated by fluctuating estrogen level, based on the observations of more PPI in women during the follicular, relative to the luteal, phase. No study has directly assessed the relationship between fluctuating hormones and PPI or PPF levels over the human ovarian cycle. To examine the roles of circulating ovarian hormones in PPI and PPF, 16 non-smoking regularly menstruating healthy women were tested during both the follicular and luteal phases on PPI and PPF and provided saliva samples for measurement of 17b-estradiol (estrogen), progesterone and testosterone. The results showed higher levels of 17b-estradiol and progesterone during the luteal, relative to the follicular, phase; and more PPI during the follicular phase and more PPF during the luteal phase with comparable startle amplitude and habituation during the two phases. A larger increase in progesterone was associated with a smaller decrease in PPI from the follicular to the luteal phase. No significant associations were found between changes in PPI/PPF and estrogen levels. The findings confirm lower PPI during the luteal, compared with the follicular, phase and suggest a role for progesterone, more specifically an antipsychotic-like PPI-restoration action of progesterone, during the luteal phase in PPI of young women.

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Section: Ovarian Hormones and Human Sensorimotor Gating V Kumari Et Almentioning

confidence: 99%

Evidence for a Role of Progesterone in Menstrual Cycle-Related Variability in Prepulse Inhibition in Healthy Young Women

Kumari

Konstantinou

Papadopoulos

et al. 2009

Neuropsychopharmacol

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“…Vasotocin and isotocin are the fish homologues of vasopressin and oxytocin, two nonapeptides closely associated with sociality in mammals (including affiliative and sexual behaviours [32]), plus social/ emotional processing, stress response modulation, learning and memory [33][34][35][36]. Oxytocin has antipsychotic properties [28,37,38] and has been shown to restore deficits in sensorimotor gating induced by MK-801 in rats [39]. The association between MK-801 exposure and isotocin/vasotocin may indicate an unexpected conservation with mammalian patterns in modulating aspects of glutamatergic signalling in fish, and may also reflect molecular stress and coping responses to cognitive disruption [33,34].…”

Section: Discussionmentioning

confidence: 99%

Testing synaptic plasticity in dynamic mate choice decisions: N -methyl d -aspartate receptor blockade disrupts female preference

Ramsey

Cummings

2014

Proc. R. Soc. B.

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Social behaviours such as mate choice require context-specific responses, often with evolutionary consequences. Increasing evidence indicates that the behavioural plasticity associated with mate choice involves learning. For example, poeciliids show age-dependent changes in female preference functions and express synaptic-plasticity-associated molecular markers during mate choice. Here, we test whether social cognition is necessary for female preference behaviour by blocking the central player in synaptic plasticity, NMDAR (N-methyl D-aspartate receptor), in a poeciliid fish, Xiphophorus nigrensis. After subchronic exposure to NMDAR antagonist MK-801, female preference behaviours towards males were dramatically reduced. Overall activity levels were unaffected, but there was a directional shift from 'social' behaviours towards neutral activity. Multivariate gene expression patterns significantly discriminated between females with normal versus disrupted plasticity processes and correlated with preference behaviours-not general activity. Furthermore, molecular patterns support a distinction between 'preference' (e.g. neuroserpin, neuroligin-3, NMDAR) and 'sociality' (isotocin and vasotocin) gene clusters, highlighting a possible conservation between NMDAR disruption and nonapeptides in modulating behaviour. Our results suggest that mate preference may involve greater social memory processing than overall sociality, and that poeciliid preference functions integrate synaptic-plasticity-oriented 'preference' pathways with overall sociality to invoke dynamic, context-specific responses towards favoured males and away from unfavoured males.

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“…Oxytocin receptor knockout mice had normal acoustic startle (Lee et al, 2008). Oxytocin also did not affect pre-pulse inhibition of startle (PPI) by itself (Feifel and Reza, 1999), but disruption of PPI by phencyclidine was enhanced in oxytocin null mice (Caldwell et al, 2009), and oxytocin and a receptor agonist, WAY-267464, reversed the disruption in PPI induced by amphetamine and MK-801 in rats (Feifel and Reza, 1999;Ring et al, 2010). Highly emotional rats that have low plasma levels of oxytocin have increased startle (Uvniis- Moberg et al, 1999).…”

Section: •mentioning

confidence: 99%

“…High doses of oxytocin had no effect on startle (Feifel and Reza, 1999), but lower doses increased startle when tested in the dark phase of the day (King et a/, 1985 ). Oxytocin null mice displayed low (Winslow et al, 2000) or normal (Caldwell et al, 2009) startle amplitudes. Oxytocin receptor knockout mice had normal acoustic startle (Lee et al, 2008).…”

Section: •mentioning

confidence: 99%

Oxytocin and Social Support as Synergistic Inhibitors of Aversive Fear Conditioning and Fear-Potentiated Startle in Male Rats

Rosen¹

2010

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE (DD-MM-YYYY) 30-09-2010 REPORT TYPE Annual DATES COVERED (From -To) TITLE AND SUBTITLE Oxytocin and Social Support as PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) AND ADDRESS(ES) PERFORMING ORGANIZATION REPORT NUMBERUniversity of Delaware Newark, Delaware 19716 SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research And Materiel Command Fort Detrick, Maryland SPONSOR/MONITOR'S REPORT 21702-5012 NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for public release; distribution unlimited SUPPLEMENTARY NOTES ABSTRACTThe purpose of the grant is to test whether exogenous oxytocin acts as an antianxiety agent and whether social support facilitates its antianxiety effects in a fear-potentiated startle paradigm. Oxytocin given systemically (0.1 µg/kg, sc) effectively reduced background anxiety, but not specific cue-potentiated fear. This was found when oxytocin was given either before fear conditioning (acquisition), immediately after fear conditioning (consolidation), or before retrieval/expression of conditioned fear-potentiated startle. Social isolation for 3 weeks potentiated startle; this was reversed by oxytocin. Intracerebroventricular infusion of oxytocin only reduced background anxiety with a very large dose (20 µg), suggesting indirect action in brain. It is concluded that oxytocin has unique antianxiety properties that reduce background and social-isolation anxiety -anxiety states not directly related to cue-specific fear, but are sustained beyond the immediate threat. Oxytocin might be promising as a drug with novel benefits for patients with PTSD. Two additional experiments demonstrated that oxtyocin did not merely reduce the ability to startle and that oxtyocin's effect was not due to reduction of contextually conditioned fear. We concluded oxytocin has a novel antianxiety profile that targets background anxiety -an anxiety state not directly related to cue--specific or contextual fear, but sustained beyond the immediate threat. Preliminary forms of this research were also presented at two meetings. The abstracts are in Appendix...

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Oxytocin as a natural antipsychotic: a study using oxytocin knockout mice

Cited by 97 publications

References 81 publications

Evidence for a Role of Progesterone in Menstrual Cycle-Related Variability in Prepulse Inhibition in Healthy Young Women

Evidence for a Role of Progesterone in Menstrual Cycle-Related Variability in Prepulse Inhibition in Healthy Young Women

Testing synaptic plasticity in dynamic mate choice decisions: N -methyl d -aspartate receptor blockade disrupts female preference

Oxytocin and Social Support as Synergistic Inhibitors of Aversive Fear Conditioning and Fear-Potentiated Startle in Male Rats

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