Methamphetamine administration during gestation impairs maternal behavior

Previous studies demonstrated that repeated drug exposure, such as opiates or cocaine, during the gestation period attenuates maternal behavior of rats; however, it is not known whether methamphetamine (MA), a drug whose usage has increased recently, negatively affects maternal behavior as well. Therefore, the present study tested the hypothesis that repeated subcutaneous administration of MA (5 mg/kg daily) throughout the entire gestation period alters maternal behavior. Dams (control, saline-, and MA-treated) were observed with their pups in two types of tests. In the observation test, 11 types of activities and three types of nursing positions of mothers were recorded 10 times during each 50-min session for the 22-day lactation period. A decrease in nursing and active maternal behavior was found in MA-treated mothers relative to control rats. In addition, stereotypic behavior such as rearing and sniffing was increased in MA- as well as in saline-treated mothers relative to controls. All mothers, regardless of the treatment, displayed significantly less maternal behavior and more nonmaternal activities as postpartum time progressed. In the retrieval test, mothers also were tested for pup retrieval from postpartum Days 1 through 12. MA-treated mothers were slower in retrieving the first pup, returning the first pup into the nest, and returning all pups into the nest relative to controls or saline-treated mothers. Interestingly, the latency to return all pups to the nest was longer in saline-treated mothers relative to controls. In conclusion, the present study demonstrates a novel finding that MA administered during the gestation period has a negative effect on maternal behavior.     

Weaning in rats: I. Maternal behavior

Maternal behavior during the weaning period (postpartum Days 14-35) was described from continuous timelapse videorecordings of Norway rat dams and their litters. Time spent nursing declined steadily after Day 20 but persisted until Day 34, about a week longer than suggested by reports of milk transfer. Most of the decline in nursing was due to progressively fewer nursing bouts per day; milk letdowns per day were consequently diminished. Although a private feeding chamber was available to the dams, they did not use this chamber to spend more time away from the pups as weaning progressed. Instead, the dams remained with the pups in the nesting chamber but devoted increasingly less time to nursing. Subtle, progressive changes in maternal behavior are closely orchestrated and coordinated with pup development.     

Comparison of the parental behavior of pair-bonded female and male prairie voles (Microtus ochrogaster)

The behavior of primiparous lactating prairie voles (Microtus ochrogaster) and their mates individually interacting with pups was continuously assessed for 45 min after a 2-h parent-litter separation on days 3-4 and 10-11 postpartum. Both sexes were highly parental after reunion with the young, and their general pattern of behavior consisted of bouts of quiescence interspersed with bursts of heightened activity. Lactating females spent more time than males in contact with pups, and more time being quiescent, most often in the kyphotic (upright crouched) nursing posture. Even in the absence of nipples upon which the pups could suckle, males also displayed kyphosis, although for shorter durations than females. Males spent more time, however, huddled over the litter in a hunched position than their mates. In accordance with their decreased quiescence, male voles licked and carried pups more and were more exploratory than females. Compared with the first week postpartum, bouts of kyphosis were shorter during the second week postpartum for both sexes, while laying prone on the pups increased. Males spent less time licking and more time carrying older pups than younger ones, and were more exploratory during the second week postpartum. Sex differences in the parental behavior of prairie voles may reflect differences in the somatosensory stimulation that females and males receive from pups. Furthermore, the display of kyphosis by male voles indicates that the sensorimotor organization of this posture in voles differs from that of lactating rats, which require suckling stimulation for its regulation.     

Endogenous opioid facilitation of maternal memory in rats

In rats, contact with pups at parturition establishes a form of maternal memory that enables female rats to respond rapidly to pups in the future. Treatment of pregnant female rats with the long-lasting micro opioid receptor antagonist, beta-funaltrexamine (beta-FNA), prior to parturition interfered with the establishment of maternal memory. Similar treatment 3 hr postpartum resulted in disrupted retention of maternal memory that appeared nonspecific, with both drug- and vehicle-treated rats displaying a deficit. However, infusion of the opioid antagonist 24 hr postpartum had no effect on the retention of maternal memory tested 7 days later. These findings indicate that the establishment of maternal memory is mediated by endogenous opioid activity around the time of parturition.     

The effects of protein malnutrition on the behavior of rats during the suckling period.

Observations of 2 groups of dams and their litters were made every 3 hr around the clock on Days 1-20 postpartum. The dams fed either an 8% or a 25% casein diet for 5 weeks before mating and during gestation and lactation. Dams on the low protein diet spent more time in the nest actively nursing their young than did high protein dams, and they exhibited no deficits in other maternal behaviors. Five of 11 kinds of behavior developed more slowly in the undernourished pups than in the well-nourished ones, but the developmental delays were no longer than a few days. Circadian fluctuations were apparent in all of the pups' activities during the 3rd postnatal week as well as in grooming and horizontal movement, 2 behaviors that were present earlier, by 6-10 days of age.     

Oxytocin antagonism alters rat dams' oral grooming and upright posturing over pups

Studies involving intracerebral administration of antiserum or antagonists have demonstrated that central oxytocin (OT) plays a prominent role in initiating but not maintaining postpartum maternal behavior in rats. There has been little investigation, however, of OT's influence on the levels of maternal behavior exhibited during the maintenance phase. We measured rat dam behavior during the 105-min observation periods preceding and beginning 2 h after intracerebroventricular infusion of the selective OT antagonist (OTA) (1 microg), or normal saline (NS) vehicle (5 microl) on postpartum days 2-3 and 6-7. Compared to NS, OTA significantly decreased pup licking as a proportion of dams' total oral grooming, increased self-grooming, decreased the frequency of elevated upright posture over pups and increased the frequency of lying prone on pups. Quiescent, kyphotic nursing was also significantly lower in OTA-treated dams. Other components of maternal behavior were not significantly affected by OTA or NS treatment. These findings suggest that central OT may shift the focus of the dams' oral grooming from self to pups and may also facilitate elevation of dams' upright posture over pups. Acute stress responses, maternal behavior and central OT receptor binding in adult rats have been linked to the amount of maternal licking and arched back, upright nursing received during infancy. OT activity in dams' brains may influence these developmental outcomes in their offspring by selectively regulating their pup licking and crouching posture.     

Mesotelencephalic dopamine system and reproductive behavior in the female rat: effects of ventral tegmental 6-hydroxydopamine lesions on maternal and sexual responsiveness

The effects of lesions to the mesolimbic dopamine system on maternal and sexual behaviors in the female rat was assessed. Rat dams that were given ventral tegmental area microinfusions of 6-hydroxydopamine (6-OHDA) during lactation showed a persistent deficit in pup retrieval but were not impaired with respect to nursing, nest building, or maternal aggression. In addition, 6-OHDA-lesioned females failed to respond to amphetamine by showing locomotor hyperactivity. Administration of the dopamine blocker raclopride to neurologically intact dams also inhibited pup retrieval but had no effect on nursing. Females given 6-OHDA during pregnancy appeared completely unresponsive to pups, whereas no maternal deficits were seen in females that received 6-OHDA 8 weeks before parturition. Proceptive (hopping and darting) and receptive (lordosis) components of sexual behavior, assessed after ovariectomy and exogenous steroid hormone treatment, were not affected by mesolimbic 6-OHDA lesions.     

Regulation of maternal food intake and mother-pup interactions by the Y5 receptor

Neuropeptide Y (NPY) is increased in the hypothalamus during lactation. To investigate the role of the NPY Y5 receptor during lactation, an antisense oligodeoxynucleotide (ODN) targeted to the NPY Y5 receptor, an equivalent scrambled ODN or vehicle, was chronically infused into the 3rd ventricle of lactating rats from day 8 postpartum. Y5 antisense ODN treatment reduced Y5 positive cell number in the paraventricular nucleus and resulted in significant reductions in food intake and litter growth. Litters from pair-fed vehicle treated dams gained significantly more weight than the litters of Y5 antisense ODN treated dams suggesting that decreased maternal food intake is not the only mechanism involved in suppressing litter weight gain. When mother-litter interaction was examined on day 13 pp, Y5 antisense ODN treated dams spent significantly less time on the nest and had significantly shorter nest bouts. These results suggest that in addition to regulating feeding behaviour, the Y5 receptor subtype may have previously unrecognised roles in the control of nesting behaviour during lactation with subsequent effects on litter growth rates.     

Effects of food restriction during concurrent lactation and pregnancy in the rat

The ability of rat dams to cope with food restriction as well as a concurrent lactation and pregnancy was examined by varying the duration, time of onset and severity of the food restriction schedule. Groups of females impregnated in the postpartum estrus and nursing 8 pups were either allowed to feed ad lib, given 60% of an ad lib ration from days 1-7, 1-14, 8-14 or 15-21 postpartum or 40% of an ad lib ration from days 1-7. Food restriction regimens that extended through the estimated time of implantation for females nursing 8 pups (days 1-14 and 8-14) resulted in a prolongation of pregnancy. Food restriction in the first week postpartum did not result in a prolongation of pregnancy and did not affect the number of females carrying the pregnancy to term. Dams food restricted in the third week postpartum had pregnancies of the same length as ad lib females but a smaller proportion of this group gave birth to a second litter.     

Importance of mother/young contact at parturition and across lactation for the expression of maternal behavior in rabbits

We prevented mother/pup contact at parturition or across early or midlactation to investigate the importance of such interaction for maintaining maternal behavior in rabbits. When pup contact was prevented across lactation Days 1–7 or 11–17 (by anesthetizing multiparous mothers during the oxytocin-induced milk letdown; Experiment 1), nursing incidence was reduced to 40% and 83%, respectively, on the day following anesthesia withdrawal. Both groups also showed a decreased milk output, long latencies to initiate nursing, and several entrances into the nest box not associated with nursing. In Experiment 2 we prevented mother/litter contact at parturition to determine the specific role of pup contact at this time. We found a reduction in the incidence of nursing on postpartum Day 1 from 80% (in control primiparous mothers) to 33%. By contrast, 100% of both deprived and control multiparous mothers displayed nursing on Day 1. These mothers also showed the unusual behaviors found in Experiment 1 and an extemporaneous nest-building. We conclude that: (a) mother/young contact at parturition is crucial for establishing maternal responsiveness in primiparous does, (b) the experience acquired by raising a previous litter allows the retention of maternal responsiveness despite a lack of pup contact at parturition, (c) maternal responsiveness is maintained across early lactation by daily interaction with pups, and (d) interaction with pups across midlactation allows the finely tuned display of maternal behavior. © 1998 John Wiley & Sons, Inc. Dev Psychobiol 32: 101–111, 1998     

Exposure to pups influences the strength of maternal motivation in virgin female rats

Following repeated exposure to foster pups, virgin female rats acquire and eventually express a full spectrum of maternal caretaking behaviors directed toward pups. Though these behaviors are vigorous, these females are reportedly less motivated to seek out and interact with pups (i.e. maternally motivated) than parturient females during early postpartum. The present study systematically assesses how the length of pup-exposure and nature of interactions between the female-pup dyad affect maternal motivation in the virgin female rat. Virgin females were exposed to young pups consistently (24 h/day) across a prolonged period (21 days), briefly (1 h/day) across a relatively brief period (7 days), or distally (pups inaccessible in mesh bag). During final pup-exposure days, females were conditioned and tested for their preference for a pup-associated chamber (e.g. maternal motivation) using conditioned place preference. Early postpartum females provided a comparison group. Fully maternal behavior only emerged in females given prolonged pup-exposure; this behavior improved significantly over time and was maximally expressed for a duration equivalent to early postpartum. Females given brief pup-exposure expressed only emergent maternal behaviors initiated by pups; distal pup-exposure evoked pup-avoidance. Virgin females given prolonged or brief pup-exposure expressed substantial pup-associated chamber preference, with more females preferring the pup-associated chamber following longer pup-exposures in a subtle stepwise relationship. Maternal motivation was strikingly similar in prolonged pup-exposure virgin and early postpartum females. Females given distal pup-exposure completely lacked maternal motivation. Maternal behavior did not predict chamber preference. Results suggest that pup-exposure, regardless of length, is sufficient to support strong maternal motivation, whereas parity is not required.     

Effects of mother-litter separation on later maternal responsiveness in the hamster

Primiparous hamsters were permitted either 1,24, or 48 hr of contact with their own litters beginning at parturition followed by varying periods of separation from pups. A different subgroup in each of these 3 conditions was tested for maternal behavior each day starting 24 hr after litter removal. Testing for the display of retrieving and the adoption of the nursing posture using 1–2 day old foster pups continued for each condition until 2 subgroups failed to behave maternally on 2 consecutive days. Nulliparous females were similarly exposed to foster pups and tested at selected intervals; regardless of initial exposure, only 4 of 24 nulliparous animals ultimately displayed maternal behavior. Different primiparous subgroups given 1 hr of exposure were maternal on Days 2–4 postpartum but not on Days 5 or 6 while females in the 24 hr group were maternal on Days 3–5 but not on Days 7 or 8. Groups permitted 48 hr of litter stimulation were maternal through Day 15 postpartum demonstrating that the initial 24–48 hr of pup contact is essential for the development of a long-term mother-young bond.     

The control and function of maternal scent marking the Mongolian gerbil

Both scent marking frequency and nest building activity increase during pregnancy and early lactation, and then gradually fall off to prepregnancy levels by the end of lactation. Females ovariectomized two days after parturition fail to show the normal increase in marking in early lactation. In addition, ovariectomy of nonpregnant females causes a significant decline in marking frequency, thus implicating ovarian secretions in the control of female scent marking. The presence of the mother's sebum on a strange pup enhances the pup's probability of being retrieved to the nest, suggesting that scent marking aids the mother in identifying her pups. The role of the hormones of pregnancy in regulating many aspects of maternal behavior is emphasized.     

Maternal behavior of primiparous females in inbred strains of mice: a detailed descriptive analysis

In the present study, we compared the maternal and non-maternal behaviors of primiparous females in both the light and dark phases during 3 weeks postpartum in five inbred strains of mice (BALB/c, CBA/Ca, C3H/He, C57BL/6, and DBA/2) to examine the strain differences in the behaviors in detail. Generally, nursing postures (arched-back, blanket, and supine) and pup lickings (anogenital and body) occurred more frequently in the light phase, whereas nest building occurred more frequently in the dark phase. As pups grew, arched-back and blanket nursing, anogenital and body licking, and nest building decreased, but supine nursing slightly increased. The present results revealed strain-specific variations in maternal behavior. In general, BALB did not engage in maternal behavior very vigorously, but the other four strains actively did. The patterns of strain differences were not parallel between the subcomponents of nursing posture or pup licking. CBA showed more arched-back and supine nursing, and DBA showed more blanket nursing. C57 and CBA showed more anogenital licking, while C3H and DBA showed more body licking. Strain differences were also found for the changes across postpartum days in almost all behaviors. These findings provide information to examine the effects of genetic and environmental factors on the development of maternal behavior in mice.     

Dysfunctional nurturing behavior in rat dams with limited access to nesting material: a clinically relevant model for early-life stress

BACKGROUND: Early-life emotional stress may be associated with affective and cognitive disorders later in life, yet satisfactory animal models for studying the underlying mechanisms are limited. Because maternal presence and behavior critically influence molecular and behavioral stress responses in offspring, we sought to create a model of dysfunctional, fragmented maternal nurturing behavior that would, in turn, provoke chronic early-life stress in the offspring. METHODS: Sprague-Dawley rat dams' nursing and nurturing behaviors were altered by limiting their ability to create satisfactory nests during postpartum days 2-9. Maternal behavior was observed throughout the diurnal cycle, and the frequency and duration of nurturing behaviors were scored. In addition, potential stress and anxiety of the dams were assessed using behavioral, molecular and hormonal measures. RESULTS: Both the quantity and the quality of dams' care of their pups were profoundly influenced by restriction of nesting materials in their cages: licking/grooming activities decreased and the frequency of leaving the pups increased, resulting in fragmented interactions between the dams and pups. The abnormal activity patterns of the dams were accompanied by increased anxiety-like behavior in the open field, but not in the elevated plus maze tests. Additionally, dams' plasma corticosterone levels and adrenal weights were augmented, suggesting chronic stress of these dams. By the end of the limited-nesting, stress-inducing period, hypothalamic corticotropin releasing hormone (CRH) mRNA expression was reduced in the limited-nesting dams, while arginine-vasopressin (AVP) mRNA levels were not significantly affected. CONCLUSION: Limiting dams' ability to construct a nest for their pups leads to an abnormal repertoire of nurturing behaviors, possibly as a result of chronic stress and mild anxiety of the dams. Because the fragmented and aberrant maternal behavior provoked chronic stress in the pups, the limited-nesting paradigm provides a useful tool for studying the mechanisms and consequences of such early-life stress experience in the offspring.     

Alterations in the maternal behavior of rats rearing hypothyroid and hyperthyroid offspring

To determine whether maternal behavior could serve as a mediator for thyroid hormone effects on behavior, I assessed nesting, nursing, grooming, contact, and retrieval in mothers of hypothyroid, hyperthyroid, and control litters, as well as in mothers of litters receiving thyroxine replacement therapy. Females assigned to the hypothyroid and replacement therapy treatments were placed on a goitrogenic diet of 2% propylthiouracil from Day 15 of gestation to Day 22 postpartum. Hyperthyroid and replacement therapy pups were injected daily with thyroxine starting on the day of birth. The decline in nesting and nursing was delayed in hypothyroid litters whereas the decline in nesting was accelerated in hyperthyroid litters. Retrieval was not affected, but grooming of pups occurred less frequently in hypothyroid and replacement therapy litters. Maternal care received by hypothyroid pups was considered adequate. Maternal behavior may alleviate some of the effects of perinatal hypothyroidism, but does not seem to be responsible for the more severe effects of hypothyroidism.     

Hypothalamic knife cuts dissociate maternal behaviors, sexual receptivity, and estrous cyclicity in female hamsters

Female hamsters were tested for their response to pups as virgins, then received sagittal cuts either lateral to the medial preoptic area-medial anterior hypothalamus (anterior cuts) or lateral to the medial anterior hypothalamus-ventromedial nucleus (posterior cuts). Postoperatively females were tested: (a) as virgins, for changes in pup retrieval and cannibalism, (b) for mating behavior, (c) for maternal care and cannibalism of their own pups, and (d) for object hoarding. Anterior cuts converted retrieving virgins to cannibalistic ones and reduced nest builing. All females with anterior cuts cannibalized their litters within a few days of parturition. Half of these females did retrieve pups in home cage tests during the first 3 days postpartum. However, unlike controls, when tested in a neutral arena 5–6 weeks later, no pup retrieval was seen, although most would hoard objects. In contrast, posterior cuts reduced pup retrieval and cannibalism in virgins, and disrupted object hoarding. These cuts did not reduce postpartum pup retrieval, but did reduce postpartum cannibalism. Anterior cuts did not reduce sexual receptivity; posterior cuts reduced sexual receptivity without eliminating ovulation. Anterior cuts are interpreted as having a somewhat selective effect of reducing maternal responsiveness by cutting the lateral connections of neurons in the medial anterior hypothalamus and adjacent medial preoptic area, while posterior cuts disrupt sexual receptivity by cutting lateral connections of the ventromedial hypothalamus which travel in the region of the supraoptic commissures     

Amygdaloid inhibition of maternal behavior in the nulliparous female rat

In the first experiment, the effects of lesions of (1) the amygdala, (2) its major efferent projection system, the stria terminalis or (3) other non-limbic brain sites on the induction of maternal behavior in the nulliparous female rat were investigated. Animals sustaining lesions of either the amygdala or the stria terminalis became maternal more rapidly than did control animals. In the second study the effects of lesions to different portions of the amygdala on both maternal and fear responding were investigated. It was found that animals sustaining damage to the corticomedial amygdaloid nuclei became maternal more quickly than did animals sustaining either basolateral amygdaloid damage or no amygdaloid damage. Also in comparison to lesioned controls, animals with lesions of the amygdala showed reduced ‘fearfulness’ on a number of fear-mediated tasks. The third study attempted to interrelate fear responsiveness and maternal behavior by observing nulliparous animals with amygdaloid or stria terminalis lesions for their responses to unfamiliar foster pups placed daily into their preferred nesting quadrant. While control animals actively avoided pups placed into their nest sites (by moving their nest site to another quadrant of the cage), animals with amygdaloid lesions or lesions of the stria terminalis, did not. These results are interpreted to mean that nulliparous females generally do not respond maternally to pups because these females are, in general, more neophobic than parturient females and they tend to find pups and their novel odors, aversive. This aspect of their behavior is likely mediated by the amygdala. These data are discussed in terms of their relevance to the rapid maternal responsiveness normally shown by the female at parturition.     

Experience with pups sustains maternal responding in postpartum rats

In these studies, we investigated the sustaining of postpartum maternal responsiveness through pup experience. In the first study, females were tested for maternal behavior at various times after pregnancy termination by Caesarean section (CS) at term. The females remained rapidly responsive to young for 7 days after pregnancy termination, but were no more responsive than virgins after 10 days. In the second study, females were allowed varying times of complete access to pups, beginning 24 hours after CS, and were tested for maternal behavior 10 days later. Females who retrieved and cared for pups for 30 minutes during exposure, remained rapidly maternal 10 days after CS; those who were allowed only 15 minutes of caring for pups did not. In the third study, females received 24 hours of exposure to distal sensory stimuli from pups, beginning 24 hours after CS. The proportion of females who became maternal within 24 hours of the beginning of maternal testing, 10 days after CS, was greater than that among females who received no exposure to pups.     

Maternal care alterations induced by repeated ethanol leads to heightened consumption of the drug and motor impairment during adolescence: a dose-response analysis

Maternal ethanol exposure during lactation induces behavioral alterations in offspring, including disruptions in motor skills and heightened ethanol ingestion during adolescence. These behavioral outcomes appear to partially depend on ethanol-induced disruptions in maternal care. The present study assessed motor skills and ethanol intake in adolescent rats raised by dams that had been repeatedly given ethanol during lactation. Female rats (postpartum days [PDs] 3-13) were administered ethanol (0.5, 1.5, or 2.5 g/kg) or vehicle every other day and allowed to freely interact with their pups. During adolescence, the offspring were evaluated for motor coordination (accelerating rotarod test) and oral ethanol self administration. The lowest maternal ethanol dose (0.5 g/kg) mildly affected motor performance, whereas the higher doses (1.5 and 2.5 g/kg) resulted in motor coordination impairment and greater ethanol intake. Maternal care behavior was affected by ethanol in a dose-dependent fashion. These results indicate that early experience with ethanol during lactation, even when the drug dosage is kept relatively low, leads to long-term consequences in offspring. Dose-response effects on maternal care behavior (i.e., nest building, crouching) may underlie disruptions in motor development and greater ethanol intake resulting from these early ethanol experiences.