Oxytocin microinjected into the central amygdaloid nuclei exerts anti-aggressive effects in male rats

Calcagnoli, Federica; Stubbendorff, Christine; Meyer, Neele; Boer, Sietse F. de; Althaus, Monika; Koolhaas, Jaap M.

doi:10.1016/j.neuropharm.2014.11.012

Cited by 72 publications

(39 citation statements)

References 77 publications

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“…Hence, research in the past decade has revolved around elucidating the precise role of OXT on social and aggressive behaviors in rodents and many other animal species. Our ethopharmacological studies in WTG rats have clearly shown that both acute and chronic enhancement of brain OXTergic function, using intraventricular [198], intracerebral [199], and even intranasal administration routes [87], produced marked anti-aggressive and pro-social affiliative effects that are dose-dependent, behavior-and receptorselective and long-lasting. Interestingly, these behavioral changes are strongly moderated by the individual's basal level of aggressiveness, suggesting an inverse relationship between traitlike aggressiveness and endogenous brain OXTergic signaling.…”

Section: Vasopressin and Oxytocinmentioning

confidence: 81%

“…Indeed, several studies in our wild-type rats and artificially selected SAL and LAL mice show a widespread central nervous differentiation between the high and low aggressive extremes, for example at the level of the oxytocinergic modulation of the central nucleus of the amygdala [199], the vasopressinergic neurons in the bed nucleus of the stria terminalis and its innervation (density) of the lateral septum [128] and the suprachiasmatic nucleus [129], the auto-inhibitory control of serotonin neurotransmission [130], and striatal dopaminergic mechanisms [131]. Hence, these may be considered as a suite of correlated neurobiological trait characteristics, which in concert may determine the appropriate behavioral and physiological response to environmental challenges.…”

Section: Neuronal Activation-patterns As Observed With C-fos Studiesmentioning

confidence: 95%

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The neurobiology of offensive aggression: Revealing a modular view

Boer

Olivier

Veening

et al. 2015

Physiology & Behavior

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Section: Vasopressin and Oxytocinmentioning

confidence: 81%

Section: Neuronal Activation-patterns As Observed With C-fos Studiesmentioning

confidence: 95%

The neurobiology of offensive aggression: Revealing a modular view

Boer

Olivier

Veening

et al. 2015

Physiology & Behavior

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“…Given the key role of the OT system in the CeA in mediating incentive learning and emotion processing (Balleine and Killcross, 2006; Ledoux, 2000), fear and anxiety responses (Bale et al, 2001; Viviani et al, 2011; Knobloch et al, 2012; Lahoud and Maroun, 2013; László et al, 2016), and aggression in rodents (Lubin et al, 2003; Bosch et al, 2005; Consiglio et al, 2005; Calcagnoli et al, 2015), it is surprising that, to the best of our knowledge, we are the first to compare the role of the OT system in the CeA between males and females. This comparison is important given that human studies demonstrated that OT modulates amygdala function differently in men and women.…”

Section: Discussionmentioning

confidence: 99%

“…Importantly, previous studies have implicated the OT system in both the MeA and CeA in mediating social behaviors, further supporting our hypothesis that these amygdala subregions may be involved in modulating social interest. For example, OT in the MeA is known to facilitate social approach and social recognition (Arakawa et al, 2010; Lukas et al, 2013), and OT in the CeA has been implicated in maternal and intermale aggression (Lubin et al, 2003; Bosch et al, 2005; Consiglio et al, 2005; Calcagnoli et al, 2015). However, comparisons between males and females regarding the role of OT in these amygdala subregions in the regulation of social behavior is largely lacking.…”

Section: Introductionmentioning

confidence: 99%

Role of the oxytocin system in amygdala subregions in the regulation of social interest in male and female rats

et al. 2016

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We previously found that oxytocin (OT) receptor (OTR) binding density in the medial amygdala (MeA) correlated positively with social interest (i.e., the motivation to investigate a conspecific) in male rats, while OTR binding density in the central amygdala (CeA) correlated negatively with social interest in female rats. Here, we determined the causal involvement of OTR in the MeA and CeA in the sex-specific regulation of social interest in adult rats by injecting an OTR antagonist (5 ng/0.5 µl/side) or OT (100 pg/0.5 µl/side) before the social interest test (4-min same-sex juvenile exposure). OTR blockade in the CeA decreased social interest in males but not females, while all other treatments had no behavioral effect. To further explore the sex-specific involvement of the OT system in the CeA in social interest, we used in vivo microdialysis to determine possible sex differences in endogenous OT release in the CeA during social interest. Interestingly, males and females showed similar levels of extracellular OT release at baseline and during social interest, suggesting that factors other than local OT release mediate the sex-specific role of CeA-OTR in social interest. Moreover, we found a positive correlation between CeA-OT release and social investigation time in females. This was further reflected by reduced CeA-OT release during social interest in females that expressed low compared to high social interest. We discuss the possibility that this reduction in OT release may be a consequence, rather than a cause, of exposure to a social stimulus. Overall, our findings show for the first time that extracellular OT release in the CeA is similar between males and females and that OTR in the CeA plays a causal role in the regulation of social interest towards juvenile conspecifics in males.

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“…This could be because the receptors facilitating or inhibiting aggression are segregated anatomically. For example, OT acting in the central amygdala inhibits male aggression [79] while AVP acting in the anterior hypothalamus facilitates aggression [80]. More direct anatomical comparisons are needed to fully understand these effects.…”

Section: Short Term Effects Of Defeat On Ot and Avp: Similarities mentioning

confidence: 99%

Sex differences in the effects of social defeat on brain and behavior in the California mouse: Insights from a monogamous rodent

Steinman

Trainor

2017

Seminars in Cell & Developmental Biology

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Women are nearly twice as likely as men to be diagnosed with major depressive disorder, yet the use of female animal models in studying the biological basis of depression lags behind that of males. The social defeat model uses social stress to generate depression-like symptoms in order to study the neurobiological mechanisms. In general, social defeat is difficult to apply in female rodents. However, male and female California mice (Peromyscus californicus) are territorial. This allows defeat to be studied in both sexes. Males exposed to defeat tend to exhibit proactive coping mechanisms and demonstrate aggression and reduced cognitive flexibility. Females exposed to defeat engage more in reactive coping mechanisms which is highlighted by social avoidance and low aggression. Importantly, effects of defeat on social interaction behavior in females is independent of adult gonadal steroids. These behavioral phenotypes are associated with sex-specific changes in arginine vasopressin (AVP) and oxytocin (OT), closely related peptides that regulate social behavior and stress reactivity. In brain regions associated with stress responses and social behavior, defeat induced long term decreases in AVP activity and increases in OT activity in males and females respectively. Intranasal OT administration was shown to mimic the effects of defeat-induced increases in endogenous OT activity, causing social withdrawal in undefeated females. This suggests that inhibition of OT activity could reduce the impact of stress on behavior in females. These results highlight the value of maintaining diverse rodent models in the search for sex-specific pharmacological approaches to treating mood disorders.

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Oxytocin microinjected into the central amygdaloid nuclei exerts anti-aggressive effects in male rats

Cited by 72 publications

References 77 publications

The neurobiology of offensive aggression: Revealing a modular view

The neurobiology of offensive aggression: Revealing a modular view

Role of the oxytocin system in amygdala subregions in the regulation of social interest in male and female rats

Sex differences in the effects of social defeat on brain and behavior in the California mouse: Insights from a monogamous rodent

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