Corticosterone Synthesis Inhibitor Metyrapone Preserves Changes in Maternal Behavior and Neuroendocrine Responses during Immunological Challenge in Lactating Rats

Abstract

Lactation is associated with profound behavioral and physiological adaptations in the mother that support reproductive success. These include neuroendocrine adaptation to stress that reduces anxiety-related behavior and emotional responsiveness. However, the way in which endogenous glucocorticoids secreted during immunological challenge influence the neuroendocrine system and behavior of lactating rats is not well understood. To evaluate the effects of glucocorticoids on the neuroendocrine response to suckling, maternal behavior and maternal anxiolysis, lactating female rats were treated with vehicle or metyrapone prior to the administration of a saline solution or a lipopolysaccharide (LPS) solution. LPS treatment reduced oxytocin and prolactin secretion during suckling and affected a variety of maternal behaviors, such as increasing the latency of retrieval a new nest, decreasing the number of pups gathered to the nest, increasing the latency of retrieving the first pup and decreasing the percentage of time spent in the arched-nursing position. In addition, the LPS treatment increased the baseline and avoidance latencies in an elevated T-maze. Pretreatment with metyrapone counteracted effects produced by LPS, including hormonal and behavioral responses in lactating rats. Taken together, our results indicate that stress induced by LPS treatment attenuates the neuroendocrine response to suckling, followed by disruption of maternal behavior and maternal anxiolysis in lactating female rats. These changes may be due to corticosterone release, as evidenced by the reversal of behavioral and neuroendocrine responses after immunological challenge in lactating rats that had been pretreated with metyrapone.

Microbial lysate upregulates host oxytocin

“…This finding is in line with the known role of oxytocin in improving social and non-social behaviors, and dampening anxiety, stress and depression (Baribeau and Anagnostou, 2015; Carter, 2014; Feldman et al, 2016). It is also consistent with previous reports describing the oxytocin-corticosterone interplay in rodent models of both social (Burkett et al, 2016; Wang et al, 2012) and non-social- related stress (Cohen et al, 2010; Smith et al, 2016a; Stanic et al, 2016; Vilela et al, 2013). It will be interesting to investigate roles for L. reuteri in stress-induced corticosterone levels and animal behaviors.…”

“…An inverse relationship exists, in general, between systemic levels of oxytocin and stress-related hormones cortisol and corticosterone (Burkett et al, 2016; Cohen et al, 2010; Smith et al, 2016a; Stanic et al, 2016; Vilela et al, 2013; Wang et al, 2012). Finding that oral L. reuteri therapy increased circulating levels of oxytocin in our animal model, we theorized that L. reuteri associated with better maternal care and nursing behavior may also down-regulate stress levels in host animals.…”

Central corticosterone disrupts behavioral and neuroendocrine responses during lactation

“…After an additional 30 min, the pups were placed back in their home cages on the side opposite the location of the previous nest, and the dam's behavior was filmed for the next 30 min. As previously described, we analyzed multiple parameters, including the retrieval latency for each pup, the number of pups brought to the nest, time spent licking the pups and percentage of time spent in the arched-nursing position [10,15].…”

“…Furthermore, acute administration of LPS (a component of gram-negative bacterial cells) on day 6 http://dx.doi.org/10.1016/j.neulet.2015.08.018 0304-3940/© 2015 Elsevier Ireland Ltd. All rights reserved. of lactation has been shown to reduce oxytocin and prolactin levels and suppress maternal behavior, likely via an increase in plasma levels of corticosterone [10]. However, the effect of acute administration of corticosterone on neuroendocrine responses has not been well studied.…”

“…The MPOA is an additional site important for oxytocin-mediated maternal care. Physical interaction with pups, with or without suckling, elicits an increased number of c-Fosimmunoreactive nuclei in the MPOA [10,11]. Although these areas are known to be key for the initiation and maintenance of maternal behavior, and stress has been shown to reduce the secretion of oxytocin, studies of the effect of corticosterone on neuronal activation in these areas have not yet been performed.…”