Brain oxytocin correlates with maternal aggression: Link to anxiety

Institute of Zoology, University of Regensburg, 93040 Regensburg, Germany.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 08/2005; 25(29):6807-15. DOI: 10.1523/JNEUROSCI.1342-05.2005
Source: PubMed


The oxytocinergic system is critically involved in the regulation of maternal behavior, which includes maternal aggression. Because aggression has been linked to anxiety, we investigated the maternal aggression and the role of brain oxytocin in lactating Wistar rats selectively bred for high anxiety-related behavior (HAB) or low anxiety-related behavior (LAB) during the 10 min maternal defense test. HAB dams displayed more maternal aggression against a virgin intruder compared with LAB dams, resulting in more defensive behavior and higher anxiety of HAB-defeated virgins. The different levels of aggression were accompanied by opposite oxytocin release patterns within the paraventricular nucleus (PVN; HAB, increase; LAB, decrease). Furthermore, oxytocin release was higher within the central nucleus of the amygdala (CeA) of HAB dams compared with LABs. A direct correlation between the offensive behavior displayed during the maternal defense test and local oxytocin release was found in both the PVN and CeA. Using retrodialysis, blockade of endogenous oxytocin action by infusion of an oxytocin receptor antagonist (des-Gly-NH2,d(CH2)5[Tyr(Me)2,Thr4]OVT) into the PVN or CeA reduced maternal aggression of HAB dams, whereas infusion of synthetic oxytocin into the PVN tended to increase aggression toward the intruder in LAB dams. There were no significant differences in oxytocin receptor mRNA expression or oxytocin receptor binding between lactating HAB and LAB dams. Therefore, differences in intracerebral release patterns of oxytocin, rather than differences at the level of oxytocin receptors, are critical for the regulation of maternal aggressive behavior.

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Available from: Simone L Meddle
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    • "Studies have shown that intranasal administration of OT in humans influences social information processing, with effects at both behavioral and neural levels [7]. OT has been reported to affect attachment [8], social exploration and memory [9], [10], aggression and anxiety [11], [12], emotion biases [13], and trust [7]. From neuroimaging studies, OT has been shown to modulate amygdala activity in response to threatening social stimuli [14], pain [15], and emotional faces [16]. "
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    ABSTRACT: Oxytocin (OT) in the central nervous system (CNS) influences social cognition and behavior, making it a candidate for treating clinical disorders such as schizophrenia and autism. Intranasal administration has been proposed as a possible route of delivery to the CNS for molecules like OT. While intranasal administration of OT influences social cognition and behavior, it is not well established whether this is an effective means for delivering OT to CNS targets. We administered OT or its vehicle (saline) to 15 primates (Macaca mulatta), using either intranasal spray or a nebulizer, and measured OT concentration changes in the cerebral spinal fluid (CSF) and in blood. All subjects received both delivery methods and both drug conditions. Baseline samples of blood and CSF were taken immediately before drug administration. Blood was collected every 10 minutes after administration for 40 minutes and CSF was collected once post-delivery, at the 40 minutes time point. We found that intranasal administration of exogenous OT increased concentrations in both CSF and plasma compared to saline. Both delivery methods resulted in similar elevations of OT concentration in CSF, while the changes in plasma OT concentration were greater after nasal spray compared to nebulizer. In conclusion our study provides evidence that both nebulizer and nasal spray OT administration can elevate CSF OT levels.
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    • "Like maternal care, it has been suggested that heightened aggression may too depend on a reduction in anxiety such that a less anxious rat will be less hesitant to attack a potentially threatening and normally fear-evoking stimulus (Lonstein et al., 1998; Caughey et al., 2011). Although the hypothesis that heightened aggression during the postpartum period requires a concomitant reduction in fear and anxiety is logical , there are numerous examples where such a simple association does not exist (Boccia and Pedersen, 2001; Bosch et al., 2005; Lonstein, 2005b) including the present results showing higher levels of aggression along with low and high levels of anxiety following administration of the OTR-A at low and high doses, respectively. Thus, even though reduced anxiety is often found in postpartum rodents, it seems that in many cases it is neither sufficient nor necessary for their heightened maternal responsiveness or aggression (Lonstein, 2005b, 2007). "
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    ABSTRACT: The neuropeptide oxytocin (OT) acts on a widespread network of brain regions to regulate numerous behavioral adaptations during the postpartum period including maternal care, maternal aggression, and anxiety. In the present study, we examined whether this network also includes the medial prefrontal cortex (mPFC). We found that bilateral infusion of a highly specific oxytocin receptor antagonist (OTR-A) into the prelimbic (PL) region of the mPFC increased anxiety-like behavior in postpartum, but not virgin, females. In addition, OTR blockade in the postpartum mPFC impaired maternal care behaviors and enhanced maternal aggression. Overall, these results suggest that OT in the mPFC modulates maternal care and aggression, as well as anxiety-like behavior, during the postpartum period. Although the relationship among these behaviors is complicated and further investigation is required to refine our understanding of OT actions in the maternal mPFC, these data nonetheless provide new insights into neural circuitry of OT-mediated postpartum behaviors.
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    • "These have suggested that oxytocin's primary function include an in-group " tendand-defend " response, such as in-group favoritism or parochial cooperation, based on the categorization of others into in-group and out-group categories (De Dreu, 2012). In rodents, it was previously reported that maternal aggression against a virgin intruder was positively correlated with oxytocin release in the paraventricular nucleus in rats selectively bred for high anxiety-related behaviors, and pharmacological blockade of oxytocin's action reduced maternal aggression (Bosch et al., 2005). These findings indicated that oxytocin promoted aggression in certain situation in rodents. "
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    ABSTRACT: In humans, oxytocin has been shown to be involved in in-group cooperative behaviors and out-group aggression. Studies have also demonstrated that oxytocin plays a pivotal role in social recognition. However, no empirical research has investigated the effect of oxytocin on in-group and out-group aggressiveness. We employed a resident-intruder paradigm to assess the ability of resident male mice to discriminate intruder male strain differences. We found that resident male mice exhibited higher frequencies of attack bites against intruders of different strains than against intruders of their own strain. Subsequently, we examined whether the interstrain recognition was regulated by the oxytocin system using oxytocin receptor (OTR)-null mice. OTR wild-type or heterozygous residents displayed higher aggression toward intruders of a strain different from their own (C57BL/6J). On the other hand, OTR-null residents exhibited greater aggression toward intruders of the same strain compared to OTR wild-type or heterozygous residents, and aggression levels were not different compared to those exhibited toward other strains. Our findings demonstrated that the oxytocin system contributes to interstrain social recognition in territorial aggression in male mice, implying that one function of oxytocin is to promote an in-group "tend-and-defend" response, such as in-group favoritism, which could be evolutionarily conserved in mammals.
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