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

Ayers, Luke W.; Missig, Galen; Schulkin, Jay; Rosen, Jeffrey B.

doi:10.1038/npp.2011.138

Cited by 68 publications

(89 citation statements)

References 76 publications

(96 reference statements)

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“…Numerous studies in animals and humans have established that OT reduces anxiety (Ayers et al, 2011; Bale et al, 2001; Blume et al, 2008; de Oliveira et al, 2012; Feifel et al, 2011; Guastella et al, 2009; Heinrichs et al, 2003; MacDonald and Feifel, 2014; Mak et al, 2012; McCarthy et al, 1996; Ring et al, 2006; Sabihi et al, 2014b; Slattery and Neumann, 2010; Uvnas-Moberg et al, 1994; Windle et al, 1997). In rodents, the mPFC is among the brain regions implicated in the anxiolytic actions of OT (Sabihi et al, 2014a; Sabihi et al, 2014b).…”

Section: Discussionmentioning

confidence: 99%

“…OT was dissolved in 0.5 µl saline at a dose of 0.1 µg (Cg1: n = 6; PL: n = 6; IL: n = 9) or 1.0 µg (Cg1: n = 6; PL: n = 6; IL n = 10). Doses were selected based on prior studies of anxiety-like behavior using site specific administration of OT (Ayers et al, 2011; Bale et al, 2001; Lee et al, 2005; Sabihi et al, 2014b). Control rats received a 0.5 µl infusion of saline (Cg1: n = 7; PL: n = 6; IL: n = 8).…”

Section: Methodsmentioning

confidence: 99%

“…In rats and mice, exogenous OT has repeatedly been shown to attenuate anxiety-like behavior when administered peripherally or centrally (Ayers et al, 2011; Bale et al, 2001; Blume et al, 2008; Mak et al, 2012; McCarthy et al, 1996; Ring et al, 2006; Sabihi et al, 2014b; Slattery and Neumann, 2010; Uvnas-Moberg et al, 1994; Windle et al, 1997). The anxiolytic effect of OT in rodents translates to humans with several studies demonstrating that intranasal administration of OT suppresses anxiety responses in healthy individuals as well as patients with anxiety disorders (de Oliveira et al, 2012; Feifel et al, 2011; Guastella et al, 2009; Heinrichs et al, 2003; MacDonald and Feifel, 2014).…”

Section: Introductionmentioning

confidence: 99%

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Oxytocin in the medial prefrontal cortex attenuates anxiety: Anatomical and receptor specificity and mechanism of action

et al. 2017

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Numerous studies in animals and humans have established that oxytocin (OT) reduces anxiety. In rats, the prelimbic (PL) subregion of the medial prefrontal cortex (mPFC) is among the brain areas implicated in the anxiolytic actions of OT. However, questions remain about the anatomical and receptor specificity of OT and its mechanism of action. Here we assessed whether the regulation of anxiety by mPFC OT is restricted to the PL subregion and evaluated whether oxytocin receptor (OTR) activation is required for OT to have an anxiolytic effect. We also examined whether OT interacts with GABA in the mPFC to reduce anxiety and investigated the extent to which OT in the mPFC affects activation of mPFC GABA neurons as well as neuronal activation in the amygdala, a primary target of the mPFC which is part of the neural network regulating anxiety. We found that OT reduced anxiety-like behavior when delivered to the PL, but not infralimbic or anterior cingulate subregions of the mPFC. The anxiolytic effect of OT in the PL mPFC was blocked by pretreatment with an OTR, but not a vasopressin receptor antagonist as well as with a GABAA receptor antagonist. Lastly, administration of OT to the PL mPFC was accompanied by increased activation of GABA neurons in the PL mPFC and altered neuronal activation of the amygdala following anxiety testing. These results demonstrate that OT in the PL mPFC attenuates anxiety-related behavior and may do so by engaging GABAergic neurons which ultimately modulate downstream brain regions implicated in anxiety.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Oxytocin in the medial prefrontal cortex attenuates anxiety: Anatomical and receptor specificity and mechanism of action

et al. 2017

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“…Endogenous oxytocin is also directly involved in anxiolysis during the postpartum period (Bosch and Neumann, 2012) as well as in males after mating (Waldherr and Neumann, 2007). Moreover, in rats and mice, OT administered peripherally or centrally attenuates anxiety (Uvnas-Moberg et al, 1994; McCarthy et al, 1996; Windle et al, 1997; Bale et al, 2001; Ring et al, 2006; Blume et al, 2008; Yoshida et al, 2009; Ayers et al, 2011; Mak et al, 2012). The anxiolytic effects of OT are also evident in humans where intranasal administration of OT has been shown to suppress anxiety responses in healthy and clinical populations (Heinrichs et al, 2003; Guastella et al, 2010; de Oliveira et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Oxytocin in the prelimbic medial prefrontal cortex reduces anxiety-like behavior in female and male rats

Sabihi¹,

Durosko²,

Dong³

et al. 2014

Psychoneuroendocrinology

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The neuropeptide oxytocin (OT) has anxiolytic effects in rodents and humans. However, the specific brain regions where OT acts to regulate anxiety requires further investigation. The medial prefrontal cortex (mPFC) has been shown to play a role in the modulation of anxiety-related behavior. In addition, the mPFC contains OT-sensitive neurons, expresses OT receptors, and receives long range axonal projections from OT-producing neurons in the hypothalamus, suggesting that the mPFC may be a target where OT acts to diminish anxiety. To investigate this possibility, females rats were administered OT bilaterally into the prelimbic (PL) region of the mPFC and anxiety-like behavior assessed. In addition, to determine if the effects of OT on anxiety-like behavior are sex dependent and to evaluate the specificity of OT, male and female anxiety-like behavior was tested following delivery of either OT or the closely related neuropeptide arginine vasopressin (AVP) into the PL mPFC. Finally, the importance of endogenous OT in the regulation of anxiety-like behavior was examined in male and female rats that received PL infusions of an OT receptor antagonist (OTR-A). Overall, even though males and females showed some differences in their baseline levels of anxiety-like behavior, OT in the PL region of the mPFC decreased anxiety regardless of sex. In contrast, neither AVP nor an OTR-A affected anxiety-like behavior in males or females. Together, these findings suggest that although endogenous OT in the PL region of the mPFC does not influence anxiety, the PL mPFC is a site where exogenous OT may act to attenuate anxiety-related behavior independent of sex.

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“…Besides its effects in social bonding and affiliation in mammals (Lim and Young, 2006), peripheral OT is involved in female reproduction (labor and milk letdown: Blanks and Thornton, 2003;Uvnäs-Moberg et al, 2001) and anxiety reduction (Olff et al, 2013). A broadening body of evidence indicates that these central and peripheral OT pathways can be coordinated (Carson et al, 2014;Carter et al, 2007;O'Byrne et al, 1990;Ross and Young, 2009;Wotjak et al, 1998) and may exert crosslinked effects (Ayers et al, 2011;Madden and Clutton-Brock, 2011;Witt et al, 1990). Other studies indicate independent control mechanisms of central and peripheral OT secretion (Amico et al, 1990;Rosenblum et al, 2002;Seckl and Lightman, 1987).…”

mentioning

confidence: 99%

Oxytocin is associated with infant-care behavior and motivation in cooperatively breeding marmoset monkeys

Finkenwirth

Martins

Deschner

et al. 2016

Hormones and Behavior

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The neurohormone oxytocin (OT) is positively involved in the regulation of parenting and social bonding in mammals, and may thus also be important for the mediation of alloparental care. In cooperatively breeding marmosets, infants are raised in teamwork by parents and adult and subadult non-reproductive helpers (usually older siblings). Despite high intrinsic motivation, which may be mediated by hormonal priming, not all individuals are always equally able to contribute to infant-care due to competition among care-takers. Among the various care-taking behaviors, proactive food sharing may reflect motivational levels best, since it can be performed ad libitum by several individuals even if competition among surplus care-takers constrains access to infants. Our aim was to study the link between urinary OT levels and care-taking behaviors in group-living marmosets, while taking affiliation with other adults and infant age into account. Over eight reproductive cycles, 26 individuals were monitored for urinary baseline OT, care-taking behaviors (baby-licking, -grooming, -carrying, and proactive food sharing), and adult-directed affiliation. Mean OT levels were generally highest in female breeders and OT increased significantly in all individuals after birth. During early infancy, high urinary OT levels were associated with increased infant-licking but low levels of adult-affiliation, and during late infancy, with increased proactive food sharing. Our results show that, in marmoset parents and alloparents, OT is positively involved in the regulation of care-taking, thereby reflecting the changing needs during infant development. This particularly included behaviors that are more likely to reflect intrinsic care motivation, suggesting a positive link between OT and motivational regulation of infant-care. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Email: christa.finkenwirth@uzh.ch A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT AbstractThe neurohormone oxytocin (OT) is positively involved in the regulation of parenting and social bonding in mammals, and may thus also be important for the mediation of alloparental care. In cooperatively breeding marmosets, infants are raised in teamwork by parents and adult and subadult non-reproductive helpers (usually older siblings). Despite high intrinsic motivation, which may be mediated by hormonal priming, not all individuals are always equally able to contribute to infant-care due to competition among care-takers. Among the various care-taking behaviors, proactive food sharing may reflect motivational levels best, since it can be performed ad libi...

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

Cited by 68 publications

References 76 publications

Oxytocin in the medial prefrontal cortex attenuates anxiety: Anatomical and receptor specificity and mechanism of action

Oxytocin in the medial prefrontal cortex attenuates anxiety: Anatomical and receptor specificity and mechanism of action

Oxytocin in the prelimbic medial prefrontal cortex reduces anxiety-like behavior in female and male rats

Oxytocin is associated with infant-care behavior and motivation in cooperatively breeding marmoset monkeys

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