Oxytocin and behavior: Lessons from knockout mice

Caldwell, Heather K.; Aulino, Elizabeth A.; Freeman, Angela R.; Miller, Travis V.; Witchey, Shannah K.

doi:10.1002/dneu.22431

Cited by 65 publications

(51 citation statements)

References 87 publications

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“…Interestingly, also the supraoptic nucleus as well as some magnocellular neurons of the paraventricular nucleus of the hypothalamus, two brain nuclei prominently expressing oxytocin, showed a robust activation in activity-based anorexia rats. It is important to note that oxytocin has been—besides its well-defined role during pregnancy—implicated in social memory, aggression and anxiety (Caldwell et al, 2016). Whether there is a direct link between anxiety or depressiveness and physical activity as suggested in humans (Holtkamp et al, 2004) warrants further investigation.…”

Section: Discussionmentioning

confidence: 99%

Activity-Based Anorexia Reduces Body Weight without Inducing a Separate Food Intake Microstructure or Activity Phenotype in Female Rats—Mediation via an Activation of Distinct Brain Nuclei

et al. 2016

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Anorexia nervosa (AN) is accompanied by severe somatic and psychosocial complications. However, the underlying pathogenesis is poorly understood, treatment is challenging and often hampered by high relapse. Therefore, more basic research is needed to better understand the disease. Since hyperactivity often plays a role in AN, we characterized an animal model to mimic AN using restricted feeding and hyperactivity. Female Sprague-Dawley rats were divided into four groups: no activity/ad libitum feeding (ad libitum, AL, n = 9), activity/ad libitum feeding (activity, AC, n = 9), no activity/restricted feeding (RF, n = 12) and activity/restricted feeding (activity-based anorexia, ABA, n = 11). During the first week all rats were fed ad libitum, ABA and AC had access to a running wheel for 24 h/day. From week two ABA and RF only had access to food from 9:00 to 10:30 a.m. Body weight was assessed daily, activity and food intake monitored electronically, brain activation assessed using Fos immunohistochemistry at the end of the experiment. While during the first week no body weight differences were observed (p > 0.05), after food restriction RF rats showed a body weight decrease: −13% vs. day eight (p < 0.001) and vs. AC (−22%, p < 0.001) and AL (−26%, p < 0.001) that gained body weight (+10% and +13%, respectively; p < 0.001). ABA showed an additional body weight loss (−9%) compared to RF (p < 0.001) reaching a body weight loss of −22% during the 2-week restricted feeding period (p < 0.001). Food intake was greatly reduced in RF (−38%) and ABA (−41%) compared to AL (p < 0.001). Interestingly, no difference in 1.5-h food intake microstructure was observed between RF and ABA (p > 0.05). Similarly, the daily physical activity was not different between AC and ABA (p > 0.05). The investigation of Fos expression in the brain showed neuronal activation in several brain nuclei such as the supraoptic nucleus, arcuate nucleus, locus coeruleus and nucleus of the solitary tract of ABA compared to AL rats. In conclusion, ABA combining physical activity and restricted feeding likely represents a suited animal model for AN to study pathophysiological alterations and pharmacological treatment options. Nonetheless, cautious interpretation of the data is necessary since rats do not voluntarily reduce their body weight as observed in human AN.

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Section: Discussionmentioning

confidence: 99%

Activity-Based Anorexia Reduces Body Weight without Inducing a Separate Food Intake Microstructure or Activity Phenotype in Female Rats—Mediation via an Activation of Distinct Brain Nuclei

et al. 2016

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“…Tet1 Δe4-/mice display abnormal social behaviors. Due to the observed dysregulation of Npas4 and Oxtr and their roles in synaptic development and function (65,66), we wanted to test whether there would be cognitive and social deficits in Tet1 Δe4-/mice. We performed a battery of behavioral tests using multiple cohorts of backcrossed (N6) C57BL/6J mice (Supplemental Figure 7).…”

Section: Discovery Of Oxtr Gene Mrna Isoforms and Reduced Expression mentioning

confidence: 99%

Epigenetic dysregulation of Oxtr in Tet1-deficient mice has implications for neuropsychiatric disorders

Towers¹,

Tremblay²,

Chung³

et al. 2018

JCI Insight

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“…In particular, associations have been found between the genetic variation of different genes involved in the oxytocinergic system and a variety of social phenotypes in different mammalian species, e.g., mice (see Caldwell et al, 2016 for a review), primates (Staes et al, 2014), cats (Arahori et al, 2015), humans (see Ebstein et al, 2012 for a review), and dogs (Kis et al, 2014). For example, polymorphisms in the oxytocin receptor ( OXTR ) gene were associated with dogs’ proximity seeking with the owner (Kis et al, 2014), rough temperament in cats (Arahori et al, 2015), and sociability in humans (Li et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Social Behavior of Pet Dogs Is Associated with Peripheral OXTR Methylation

et al. 2017

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Oxytocin is a key modulator of emotional processing and social cognitive function. In line with this, polymorphisms of genes involved in oxytocin signaling, like the oxytocin receptor (OXTR) gene, are known to influence social behavior in various species. However, to date, no study has investigated environmental factors possibly influencing the epigenetic variation of the OXTR gene and its behavioral effects in dogs. Pet dogs form individualized and strong relationships with their owners who are central figures in the social environment of their dogs and therefore might influence the methylation levels of their OXTR gene. Here we set out to investigate whether DNA methylation within the OXTR promoter region of pet dogs is linked to their owner’s interaction style and to the social behavior of the dogs. To be able to do so, we collected buccal epithelial cells and, in Study 1, we used pyrosequencing techniques to look for differentially methylated CpG sites in the canine OXTR promoter region on a heterogeneous sample of dogs and wolves of different ages and keeping conditions. Four identified sites (at positions -727, -751, -1371, and -1383 from transcription start site) showing more than 10% methylation variation were then, in Study 2, measured in triplicate in 217 pet Border Collies previously tested for reactions to an adverse social situation (i.e., approach by a threatening human) and with available data on their owners’ interaction styles. We found that CpG methylation was significantly associated with the behavior of the dogs, in particular with the likelihood that dogs would hide behind their owner or remain passive when approached by a threatening human. On the other hand, CpG methylation was not related to the owners’ behavior but to dog sex (at position -1371). Our findings underpin the complex relationship between epigenetics and behavior and highlight the importance of including epigenetic methods in the analysis of dog behavioral development. Further research is needed to investigate which environmental factors influence the epigenetic variation of the OXTR gene.

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Oxytocin and behavior: Lessons from knockout mice

Cited by 65 publications

References 87 publications

Activity-Based Anorexia Reduces Body Weight without Inducing a Separate Food Intake Microstructure or Activity Phenotype in Female Rats—Mediation via an Activation of Distinct Brain Nuclei

Activity-Based Anorexia Reduces Body Weight without Inducing a Separate Food Intake Microstructure or Activity Phenotype in Female Rats—Mediation via an Activation of Distinct Brain Nuclei

Epigenetic dysregulation of Oxtr in Tet1-deficient mice has implications for neuropsychiatric disorders

Social Behavior of Pet Dogs Is Associated with Peripheral OXTR Methylation

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