Anne D. Mayer

HORMONAL BASIS DURING PREGNANCY FOR THE ONSET OF MATERNAL BEHAVIOR IN THE RAT

This article reviews the current state of our knowledge about the hormonal basis of maternal behavior in the rat. Considered are the ovarian hormones estrogen and progesterone, the pituitary hormones beta-endorphin and prolactin, and the hormone oxytocin, secreted by several hypothalamic nuclei and associated brain regions. The hormones of pregnancy, estrogen and progesterone, prime the female to respond to a terminal rise in estrogen that stimulates a high level of maternal responsiveness even before parturition begins. Studies on the role of prolactin, using hypophysectomy, prolactin release blockers and anterior pituitary and prolactin replacement, indicate that prolactin is required for the ovarian hormones to be effective in stimulating maternal behavior. During the latter half of pregnancy, placental lactogen may displace prolactin in this role. Although prolactin serves as a chronic stimulus for maternal behavior, it also may act over a short period. Oxytocin stimulates maternal behavior in a specific strain of rat, but not in other strains, and only when administered introcerebroventricularly (ICV) in estrogen-primed females. The decline in the high brain levels of beta-endorphin around parturition has been proposed as a requirement for the onset of maternal behavior; morphine blocks the onset of maternal behavior and disrupts ongoing maternal behavior and maternal aggression in lactating females. However, blocking beta-endorphin action at parturition interferes with pup cleaning and eating of the placenta as well.

Progress in the Study of Maternal Behavior in the Rat: Hormonal, Nonhormonal, Sensory, and Developmental Aspects

Publisher Summary This chapter discusses the progress that has been made in the study of maternal behavior in the rat with special focus on the research that has been carried out at the Institute of Animal Behavior. It describes how maternal behavior arises from the hormonal conditions that exist during pregnancy, particularly around parturition when maternal behavior normally begins. The chapter demonstrates that the maternal behavior cycle is a developmental product of hormonal events during pregnancy, especially at its termination, and of behavioral stimulation received during interactions between the mother and her young. Investigation of females whose pregnancies were terminated prematurely by hysterectomy and/or ovariectomy has shown that the rise in estrogen, primarily, is responsible for the onset of maternal behavior under these conditions. To be effective this rise must occur free of the inhibiting influence of high levels of progesterone and that the decline in progesterone in addition to its permissive action with respect to estrogen may itself facilitate a short-term increase in maternal responsiveness. The chapter further deals with postpartum stimulus factors, which regulate maternal behavior and are involved in its maintenance and eventual decline.

Decline of maternal behavior in the virgin and lactating rat.

Sensitized virgins and postpartum lactating mothers, both exhibiting maternal behavior, were given donor litters that increased in age by 1 day, for 28 days, starting at the onset of maternal behavior. Each day females were tested for maternal behavior with pups 4-8 days old: Maternal care (i.e., nursing/crouching, retrieving, nest building and licking) and maternal withdrawal, rejection, and prevention of nursing were recorded. After the ninth day, females were also tested with the progressively older pups from 10 to 28 days of age with which they were living. Virgins and lactating mothers showed generally similar patterns of maternal care although some differences were found, and they declined in maternal behavior toward the older pups in a similar manner. Maternal behavior did not decline in tests with younger pups. The results are interpreted as supporting the hypothesis that the decline as well as the maintenance of maternal behavior postpartum is nonhormonally mediated.

Hormonal factors influence the onset of maternal aggression in laboratory rats

This experiment addressed the hypothesis that aggressiveness toward conspecifics is stimulated by hormonal factors known to mediate the onset of maternal care. Subjects included both pregnant and virgin females. Sixteen-day pregnant rats were hysterectomized (H), hysterectomized-ovariectomized and injected with estrogen (HO-EB), or subjected to sham procedures. Nonpregnant females were HO-EB or sham operated. The females were sensitized by continuous exposure to pups and were judged to have initiated maternal care when all pups were retrieved and grouped, Aggressiveness was observed during 5-min intruder tests using unfamiliar males, administered (a) 10 min prior to the introduction of test pups, (b) following the first 3 hr of pup exposure, and (c) after females had initiated maternal care. The results revealed that treatments known to reduce sensitization latencies also increased aggressiveness even prior to exposure to pups. Aggressiveness was displayed before sensitization only in groups having elevated estrogen levels. After initiating maternal behavior, pregnant and pregnancy-terminated females increased further in aggressiveness whereas nonpregnant females did not. Pregnancy-terminated, HO-Oil females became aggressive (only) after initiating maternal behavior, indicating that factors other than estrogen also influence the onset of maternal aggression.

Maternal aggression in rats: Changes over pregnancy and lactation in a sprague‐dawley strain

Maternal aggression in a Sprague-Dawley strain of laboratory rat (Charles River CD) was explored from Day 1 after mating on Day 0 through Day 24 of lactation (L0-L24). Aggression toward unfamiliar male “intruders” during 10-min tests was low among nonpregnant, nonlactating females and during the first 10 days of gestation. Frequency of attack on intruders increased moderately but significantly by Gestation Day 16 (G16; Experiment 1) or G21 (Experiment 2), a prepartum phenomenon not previously reported in laboratory rats. Levels of aggression were highest, however, during the first 9 days of lactation, when attacks averaged more than 6 per 10-min session. Attacks declined sharply in frequency after L14 and by L24 did not exceed levels observed among nonpregnant females. Experiment 3 examined the importance of the test site (home cage with nest and pups, if any, vs unfamiliar cage without nest or pups) to agonistic behavior associated with pregnancy and lactation. Late pregnant females tested in a novel cage were not aggressive; however, females tested shortly after delivering their pups were highly aggressive, averaging over four attacks per 5-min session. In novel cage tests frequency of attack remained high through L4 but declined significantly by L7. These data are consistent with the hypothesis that maternal aggression at its onset is primarily under hormonal control, but becomes increasingly dependent upon external factors, presumably pup stimulation, during the postpartum period.

Differential roles of hypogastric and pelvic nerves in the analgesic and motoric effects of vaginocervical stimulation in rats

Bilateral transection of the pelvic and/or hypogastric nerves, which convey afferent activity from the reproductive tract, was performed to ascertain the role of these nerves in the analgesic and motoric effects of vaginocervical mechanostimulation (VS) in rats. Two indices of analgesia were used: tail flick latency to radiant heat (TFL) and vocalization threshold to electrical shock of the tail (Voc-T). Nerve cuts were performed at least one week prior to behavioral testing. Bilateral transection of both the pelvic and hypogastric nerves eliminated the analgesic effects of VS on the TFL and Voc-T tests. Bilateral transection of only the pelvic nerves reduced the number of rats showing maximal VS-induced elevation in TFL, without altering the effect of VS on Voc-T. By contrast, bilateral transection of only the hypogastric nerves attenuated the Voc-T-elevating effect of VS, without reducing the effect of VS on elevating TFL. The effects of VS on producing immobility, hindlimb extension and blockage of hindlimb withdrawal to foot pinch were eliminated by combined bilateral pelvic and hypogastric neurectomy. However, bilateral transection of either nerve alone did not significantly alter the efficacy of VS in producing these effects. These findings indicate that the pelvic and hypogastric nerves contribute to the immobility- and extensor-inducing, and flexor-inhibiting effects of VS, and differentially mediate the analgesia-producing effects of VS.

Prolonged estrogen-progesterone treatment of nonpregnant ovariectomized rats: Factors stimulating home-cage and maternal aggression and short-latency maternal behavior

A 16-day treatment of nonpregnant, ovariectomized rats using 5-mm Silastic implants of estradiol (E), daily injections of 4 mg of progesterone (P), and terminal injections of 5 micrograms/kg of estradiol benzoate (EB) to provide a pregnancy-like pattern of hormone exposure, stimulates (a) home-cage aggression toward unfamiliar intruder rats, (b) short-latency maternal behavior when the females are exposed continuously to pups, and (c) maternal aggression after maternal care has been initiated. Preliminary experiments examined the persistence of stimulation of aggression by the 16-day treatment in the absence of exposure to pups eliciting maternal care, and whether an abbreviated, 1-week treatment stimulates aggression equally. Subsequent experiments examined the importance of the elements of the treatment (E implants, P injections, EB injection), and whether prolonging exposure to P or E would alter its behavioral effects. The full 16-day E/P/EB treatment stimulated higher levels of home-cage and maternal aggression, and shorter maternal behavior latencies than abbreviated and partial treatments. E in combination with P or EB significantly raised home-cage aggression, whereas P alone was without effect. Administering P for 2 additional days attenuated reductions in maternal behavior latencies by E/P/EB, but did not reduce home-cage or maternal aggressiveness. Continuous exposure to E throughout testing did not affect any dependent variable. Comparing these findings to earlier data and reports suggests that hormone exposure for 2 weeks or more, and provision of P levels approaching those of pregnancy are important to the effects of the E/P/EB treatment on aggression.

Peripeduncular nucleus lesions in the rat: I. Effects on maternal aggression, lactation, and maternal behavior during pre- and postpartum periods.

Bilateral peripeduncular (PPN) lesions made on the seventh postpartum day (L7) with either radiofrequency (RF) current or N-methyl-d,l-aspartic acid (NMDA)/phosphate buffered saline (PBS) reduced maternal aggression (MA) and partially inhibited lactation without producing significant deficits in other items of maternal behavior (MB). RF-PPN lesions did not interfere with prolactin secretion, which suggests that there was deficient oxytocinergic activity. The deficit in MA was not due to interruption of afferent suckling input to the PPN: either thelectomizing females (day L6) or producing bilateral knifecuts in the mesencephalon (placed caudal to the level of the PPN; Day L7) had no effect on MA, but both procedures impaired lactation. Deficits in MA produced by RF-PPN lesions developed gradually between Days L4 and L7; lesions made either prepartum or on Day L1 did not impair MA or MB. Deficits in lactation first appeared after RF-PPN lesions on Day L1.

Effects of intranasal zinc sulfate on open field and maternal behavior in female rats

Abstract Nulliparous white rats were injected intranasally (IN) or intraperitoneally (IP) with zinc sulfate (Zn) or were injected IN with saline or air, and were induced to show maternal behavior through continuous pup exposure begun 24 or 48 hr after treatment. ZnIN and ZnIP groups all showed declines in locomotor activity and rearing in an open field. ZnIN females sniffed less and groomed more often and for more total time than ZnIP or AIR females, effects attributed to nasal irritation and impaired olfaction. Declines in activity did not appear due to systemic absorption of zinc sulfate. Induction of maternal behavior was facilitated by ZnIN but not by ZnIP. Modifications of IN injection procedures were felt to have reduced post-treatment debilitation caused by accidental aspiration of zinc sulfate.

Relationship between maternal aggression and maternal care in the rat

Aggression among female rats is almost entirely confined to the period of late pregnancy and lactation. Behaviorally it is similar to the aggression of males including piloerection and lateral attacks, but it differs in its function. Unlike male aggression which serves to establish a social hierarchy and a territory, i. e., is competitive, maternal aggression is protective, i. e., it serves to prevent predation of the mothers offspring. In this respect it is closely related temporally and causally to maternal care; if the offspring are removed maternal aggression wanes almost immediately–its function no longer exists! Studies on aggression by mothers, among rats, from the authors laboratory are reviewed and comparisons made with maternal care. As noted, maternal aggression and maternal care are closely related during the cycle of maternal behavior and they share a similar hormonal basis and possibly the effect of uterine stimulation, but maternal care requires prolactin and the decline of progesterone while maternal aggression appears independent of pituitary hormones and does not require a decline in progesterone. Maternal aggression like maternal care appears to be organized into a hormonal phase, during pregnancy, parturition, and for about a week postpartum and a nonhormonal phase thereafter. Bilateral radiofrequency lesions of the lateral midbrain peripeduncular nucleus (PPN) produce deficits in maternal aggression if made on lactation day 7 (L7), but not earlier, without producing significant deficits in maternal behavior. Experiments showed that the PPN does not mediate hormonally stimulated maternal aggression; it appears to mediate only nonhormonally stimulated maternal aggression. Studies on the role of pregnancy hormones on long-term retention of maternal aggression and the role of olfaction in maternal aggression are also reviewed.