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Impairments in the initiation of maternal behavior in oxytocin receptor knockout mice
Megan E Rich1, Emily J deCárdenas2, Heon-Jin Lee3
1Laboratory of Neuroendocrinology and Behavior, Department of Biological Sciences, Kent State University, Kent, Ohio, United States of America; School of Biomedical Sciences, Kent State University, Kent, Ohio, United States of America.
Abstract:
Oxytocin (Oxt) acting through its single receptor subtype, the Oxtr, is important for the coordination of physiology and behavior associated with parturition and maternal care. Knockout mouse models have been helpful in exploring the contributions of Oxt to maternal behavior, including total body Oxt knockout (Oxt -/-) mice, forebrain conditional Oxtr knockout (Oxtr FB/FB) mice, and total body Oxtr knockout (Oxtr -/-) mice. Since Oxtr -/- mice are unable to lactate, maternal behavior has only been examined in virgin females, or in dams within a few hours of parturition, and there have been no studies that have examined their anxiety-like and depression-like behavior following parturition. To improve our understanding of how the absence of Oxt signaling affects maternal behavior, mood and anxiety, we designed a study using Oxtr -/- mice that separated nursing behavior from other aspects of maternal care, such as licking and grooming by thelectomizing (i.e. removing the nipples) of Oxtr +/+ mice and sham-thelectomizing Oxtr -/- mice, and pairing both genotypes with a wet nurse. We then measured pup abandonment, maternal behavior, and postpartum anxiety-like and depression-like behaviors. We hypothesized that genetic disruption of the Oxtr would impact maternal care, mood and anxiety. Specifically, we predicted that Oxtr -/- dams would have impaired maternal care and increased anxiety-like and depression-like behaviors in the postpartum period. We found that Oxtr -/- dams had significantly higher levels of pup abandonment compared to controls, which is consistent with previous work in Oxtr FB/FB mice. Interestingly, Oxtr -/- dams that initiated maternal care did not differ from wildtype controls in measures of maternal behavior. We also did not find any evidence of altered anxiety-like or depressive-like behavior in the postpartum period of Oxtr -/- dams. Thus, our data suggest that Oxt lowers the threshold for the initiation of maternal behavior.
Insights
Oxytocin receptor knockout mice showed increased pup abandonment but initiated maternal care similarly to controls. This suggests oxytocin lowers the threshold for starting maternal behavior, not maintaining it.
Area of Science:
- Neuroendocrinology
- Behavioral Neuroscience
- Reproductive Biology
Background:
- Oxytocin (Oxt) and its receptor (Oxtr) are crucial for maternal care behaviors and postpartum physiology.
- Previous studies using Oxt and Oxtr knockout models have provided insights into Oxt's role in maternal behavior.
- Oxtr knockout mice cannot lactate, limiting studies on postpartum maternal behavior and mood.
Purpose of the Study:
- To investigate the specific role of oxytocin receptor signaling in maternal behavior, postpartum anxiety, and depression.
- To disentangle the effects of Oxtr signaling on the initiation versus maintenance of maternal care.
- To assess anxiety-like and depression-like behaviors in postpartum Oxtr knockout dams.
Main Methods:
- Used a novel experimental design in Oxtr knockout (Oxtr -/-) and wildtype (Oxtr +/+) mice, separating nursing from other maternal care aspects via thelectomy and wet nursing.
- Measured pup abandonment rates, maternal behaviors (licking, grooming), and postpartum anxiety- and depression-like behaviors.
- Compared Oxtr -/- dams with Oxtr +/+ controls under conditions that allowed for the assessment of maternal care initiation and maintenance.
Main Results:
- Oxtr -/- dams exhibited significantly higher levels of pup abandonment compared to controls.
- Maternal dams of both genotypes that initiated care did not differ in measures of maternal behavior (licking, grooming).
- No significant alterations in postpartum anxiety-like or depression-like behaviors were observed in Oxtr -/- dams.
Conclusions:
- Genetic disruption of the oxytocin receptor leads to increased pup abandonment.
- Oxytocin signaling appears critical for lowering the threshold for the initiation of maternal behavior, rather than its maintenance.
- The absence of Oxtr signaling does not inherently lead to increased postpartum anxiety or depression-like behaviors in this model.
