In the present study we examined whether the gene for
In the present study we examined whether the gene for estrogen receptor alpha, Esr1, plays a role in the expression of maternal memory in female rats. The approach utilized a newly developed rat Esr1 knockout (KO) rat model (Rumi et al., 2014) to evaluate whether deletion of the Esr1 LKB1 affected the induction of maternal care and the expression of maternal memory in pup-induced, nulliparous female rats. This KO approach is designed to help determine whether estrogens, through their actions on estrogen receptor-alpha, facilitate the activation as well as the retention of maternal care.
Discussion In this knockout study, latencies to initially induce home cage maternal responsiveness in the Esr1 KO rats were comparable to that found in the WT subjects. Both groups required approximately 10 days of daily pup exposure before full maternal care was established. The similarity in responsiveness differs from that reported in Esr1 KO mice (Ogawa et al., 1998) in which mice lacking the estrogen receptor alpha alleles displayed deficits in maternal as well as paternal care. It is unknown what contributes to this species difference in the role of the Esr1 gene in maternal care. It is possible that the underlying nonhormonal basis for maternal care differs between rats and mice contributed to each species response. It is established that the pituitary gland and its regulatory factors are not essential for the expression of maternal behavior in the rat (Rosenblatt, 1967). Consistent with this idea, the present study demonstrates that Esr1 including receptors located throughout the body, including the brain, are also non-essential for the display of the basic capacity to exhibit maternal care, supporting previous work by Stolzenberg and Rissman. When the subjects that responded maternally in the induction testing were tested for the retention of maternal care after 30 days of separation from foster young, both groups responded with similar reinduction latencies in home cage testing. It was somewhat surprising, however, that neither group displayed shortened latencies to respond upon reinduction testing. Latencies again averaged about 9–10 days. In fact, a small percentage of subjects failed to re-induce over the 15-day test period, results that differ from previous reports (Cohen and Bridges, 1981; Scanlan et al., 2006). When comparing responses during overnight observations during retention testing, it was noted that the Esr1 KOs had grouped and crouched over their test pups in fewer days than did the WT subjects. This, however, did not translate into shorter latencies during the 2-hour home cage test. This response may reflect a difference in motivation or perhaps activity between the pretest period and the test sessions in the Esr1 knockout animals. Slight differences did emerge between the re-induced maternal KO and WT groups in the novel cage testing following home cage testing. The maternal WT subjects appeared to display a more intense response in the novel cage testing. Specifically, WT subjects displayed a shorter latency to retrieve/carry a pup, exhibited enhanced carrying of the first pup, and had a shorter latency to engage in oral contact (mouthing) than did the Esr1 KO subjects. One interpretation of these responses is that maternal WT rats display a higher level of motivation than Esr1 KO maternal rats to engage in pup-directed behaviors. Nevertheless, comparison between the WT and Esr1 KO revealed more similarities than differences in pup-induced maternal responses. It could be that the Esr1 gene may modulate the maternal response of the subject in more challenging environmental conditions but that the basic capacity to display both the induction and re-induction of maternal care in the home cage is quite comparable. Novel environment maternal responding is mediated by both the aversiveness of the environment and pup salience, and estrogen receptors are implicated in the neuroendocrine and behavioral responses to stress (Handa et al., 2012). Perhaps test conditions that induce a more robust stress response and demand a greater level of motivation are required to delineate potential differences in the stress response and/or maternal care between animals lacking the Esr1 gene and those having the normal complement of alleles. It is possible that the current novel cage differences were mediated by a more substantial stress response in the Esr1 KO females.