Impairments in the initiation of maternal behavior in oxytocin receptor knockout mice

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.

Figure 1. Increased pup abandonment was observed in Oxtr −/− dams compared to Oxtr +/+ dams.

67% of Oxtr −/− females cannibalized or abandoned their pups by PND1 compared to 20% of Oxtr +/+ females. *two-tailed p = 0.021.

Figure 2. Latency to retrieve the first pup by Oxtr +/+ and Oxtr −/− dams on PND1-3.

There were no genotypic differences in the latency to retrieve the first pup across the 3 days of testing.

Figure 3. Oxtr −/− dams had normal anxiety-like and depression-like behavior, as measured by (A) percent time in the open arms compared to Oxtr +/+ dams in an elevated plus maze on PND4, (B) in percent time in the inner arena in an open field test on PND5 (B), and (C) in the percent time swimming in a forced swim test.