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Finasteride delays the onset of maternal behavior in primigravid rats.

The inhibitory actions of progesterone on maternal behavior may be due to its metabolite, allopregnanolone. Allopregnanolone has been shown to mediate some cognitive, anxiolytic and sex behavior actions of progesterone. The objectives of the present study were to determine: first, if the administration of finasteride, a 5 alpha-reductase inhibitor, will stimulate fast-latency maternal behavior in primigravid rats and, second, to assess whether finasteride increases anxiety-like behaviors and alters circulating progesterone levels during pregnancy. In Experiment 1, primigravid Sprague-Dawley females received daily injections of either finasteride (50 mg/kg, s.c.) or vehicle (20% ethanol in sesame oil) starting on day 12 of gestation and continuing until parturition. On day 15 of gestation, daily maternal behavior testing began. In contrast to expectation, administration of finasteride significantly delayed the onset of maternal behavior compared to vehicle-treated rats (P < 0.05). In addition, the percentage of animals responding maternally on each test day tended to be lower for the finasteride-treated group (day 19, P = 0.078). In Experiment 2, a separate group of animals received daily finasteride injections starting on day 12 of gestation. On day 15, females were tested on the elevated plus maze and were then implanted with jugular catheters. Blood samples were taken daily (0900-1100 h) on days 17, 18 and 19 of gestation. Finasteride-treated females displayed significantly more anxiety-like behaviors in the elevated plus maze (P < 0.05). In addition, finasteride administration maintained elevated plasma progesterone levels compared to vehicle-treated controls (P = 0.03). These results suggest that the inhibition of maternal behavior by progesterone during pregnancy is not due to its conversion to allopregnanolone.

5-alpha Reductase Inhibitors↗

Possible role for endogenous oxytocin in estrogen-facilitated maternal behavior in rats.

Intracerebroventricular (i.c.v.) infusions of oxytocin (OXY) induce short-latency maternal behavior in estrogen-primed virgin rats. To investigate if brain OXY might have a role in the onset of maternal behavior at parturition, we have used both antisera to OXY and an analog antagonist of OXY, d(CH2)5-8-ornithine-vasotocin, to reduce the activity of endogenous OXY in a pregnancy-terminated preparation which yields reliable short-latency maternal behavior. Sprague-Dawley rats with lateral ventricle cannulae were ovariectomized and hysterectomized on day 16 of gestation; maternal behavior was stimulated by a s.c. injection of estradiol benzoate (EB). Effects of the i.c.v. infusion of antisera to OXY or of the i.c.v. infusion of d(CH2)5-8-ornithine-vasotocin on the latency to respond to pups were tested by presenting pups 48 h after surgery and EB treatment. Behavioral observations were made for the next 5 h and periodically over the next 5 days. Groups receiving either the antisera to OXY or the analog antagonist had significantly longer latencies to respond to pups than did control groups. In a separate experiment, i.c.v. infusion of d(CH2)5-8-ornithine-vasotocin was shown to have no effect on the performance of maternal behavior in lactating rats 5 days postpartum. These results suggest that OXY may have a role in promoting short-latency maternal behavior in steroid-primed female rats, but that it is probably not involved in sustaining this behavior during lactation.

Animals↗

Behavioral outcome of preschoolers exposed prenatally to cocaine: role of maternal behavioral health.

OBJECTIVE: To examine the impact of prenatal cocaine exposure and maternal behavioral health (recent drug use and psychological functioning) on child behavior at age 5 years. METHOD: In this longitudinal investigation, maternal report of child behavior was assessed using the Achenbach Child Behavior Checklist (CBCL) in 140 cocaine-exposed and 181 noncocaine-exposed (61 alcohol, tobacco, and/or marijuana-exposed, and 120 nondrug-exposed) low-income, African American children. Structural equation modeling was used to estimate suspected causal relationships between indicators of maternal behavioral health at 5-year follow-up, according to self-report on a modified Addiction Severity Index (ASI) and CBCL scores. RESULTS: Prenatal cocaine exposure was not related to child behavior at age 5. Recent maternal drug use and psychological functioning had relationships with CBCL Internalizing and Externalizing scores. However, when considered within a combined model, only maternal psychological functioning remained significant. CONCLUSIONS: Findings highlight the importance of maternal functioning in the behavioral outcome of children exposed prenatally to cocaine.

Black or African American↗

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.

Animals↗

Null mutation of the prolactin receptor gene produces a defect in maternal behavior.

We have studied pup-directed maternal behavior in mice carrying a germ line null mutation of the PRL receptor (PRLR) gene. Homozygous mutant and heterozygous mutant nulliparous females show a deficiency in pup-induced maternal behavior. Moreover, primiparous heterozygous females exhibit a profound deficit in maternal care when challenged with foster pups. Morris maze studies revealed normal configural learning in the heterozygous and homozygous animals. Eating, locomotor activity, sexual behavior, and exploration (all processes regulated by the hypothalamus) are normal in PRLR mutant mice. Olfactory function was tested in an aversive conditioning paradigm, results indicating that heterozygous and homozygous PRLR mutant mice are not anosmic. These studies clearly establish the PRLR as a regulator of maternal behavior.

Animals↗

Anatomical identification of neurons in selected brain regions associated with maternal behavior deficits induced by knife cuts of the lateral hypothalamus in rats.

The present experiment identified neurons associated with maternal behavior deficits induced by damage to the lateral hypothalamus (LH) in rats. Fully maternal lactating rats received bilateral coronal knife cuts through either the dorsal or ventral LH at the level of the ventromedial nucleus. The blade of the wire knife used to make the cuts was coated with horseradish peroxidase (HRP). The maternal behavior of all females was studied for 4 days postoperatively and then the brains were processed for the localization of neurons retrogradely filled with HRP. The analysis focused on those brain regions thought to be important for maternal behavior. The dorsal LH cuts severely disrupted maternal behavior while the ventral LH cuts did not. The ventral cuts labeled more medial preoptic area (MPOA) and septal-diagonal band neurons with HRP than did the dorsal cuts. The dorsal LH cuts labeled more neurons with HRP in the lateral preoptic area (LPOA), magnocellular preoptic area, bed nucleus of the stria terminalis, ventral tegmental area (VTA), substantia nigra, and central gray than did the ventral cuts. Previous research has suggested that the lateral efferents of the MPOA interact with the VTA in the control of maternal behavior. The results of the present experiment suggest that MPOA axons which descend directly to the brainstem via the ventral LH are not essential for maternal behavior. Our results are consistent with the view that an MPOA-to-LPOA-to-VTA circuit may be important for maternal behavior.

Animals↗

Medial preoptic area and onset of maternal behavior in the rat.

The present series of experiments examined whether the medial preoptic area (MPOA) is involved in the onset of maternal behavior in the rat. Previously, the MPOA had been shown to be important in the maintenance of maternal behavior in the lactating rat. The first experiment investigated whether estradiol benzoate (EB) acts on the MPOA to facilitate the onset of maternal behavior in the 16-day pregnant, hysterectomized, and ovariectomized female rat. Such rats when given EB implants in the MPOA had significantly shorter latencies for the onset of maternal behavior than had females implanted with cholesterol in the MPOA or with EB in the ventromedial hypothalamus, in mammillary bodies, or under the skin. A second experiment showed that estrogen-induced prolactin release was not involved in this facilitation. A third experiment indicated that MPOA lesions disrupt the onset of maternal behavior that is induced by pup stimulation in virgin females. It was concluded that the MPOA is involved not only in the maintenance of maternal behavior but in the hormonally mediated onset of maternal behavior and the onset of maternal behavior induced in virgin females by pup stimulation.

Animals↗

Immobility in the swim test and observations of maternal behavior in lactating Flinders sensitive line rats.

In order to elucidate the relationship between maternal behavior and depression, the Flinders sensitive line (FSL) model of depression was studied and compared to Sprague-Dawley (SD) controls. Immobility in the swim test was measured, as an index for depressive-like behavior, and frequencies of maternal and non-maternal behaviors were recorded using short un-intrusive observations in the home cage. Lactating FSL rats displayed higher levels of immobility in the swim test compared to controls, indicating depressive-like behavior. In addition, compared to SD rats, FSL dams showed less frequent pup licking and non-nutritive contact with pups during the first and third weeks of lactation. In the third postpartum week, FSL dams showed less frequent nursing postures and more frequent self-directed behaviors. Thus, lactating FSL dams exhibit both depressed-like behavior and some abnormalities in maternal behavior.

Analysis of Variance↗

Effects of brain antiestrogen implants on maternal behavior and on postpartum estrus in pregnant rats.

To test the hypothesis that the onset of maternal behavior is stimulated by estrogen, we examined the effects of medial preoptic area (MPOA) or ventromedial hypothalamus (VMH) implants of the antiestrogen 4-hydroxytamoxifen (OH-TAM) on pre- and postpartum maternal behavior and on postpartum estrus in rats. On day 20 of pregnancy, animals were implanted bilaterally with OH-TAM or cholesterol cannulae into MPOA or VMH. Unilateral cannulae of OH-TAM were also placed into MPOA. Females were tested with newborn pups for the onset of immediate retrieval, prepartum, at noon on day 21, at midnight of the day 21, and 1 day following parturition (which occurred on day 22). On the evening of parturition, implanted animals were tested with stimulus males for the occurrence of postpartum estrus. In order to examine the influence of estrogen on maternal behavior in the absence of parturitional experience, antiestrogen-implanted animals were delivered surgically (cesarean section) and were observed for the display of maternal behavior at various times after surgery. At noon of day 21, only a few animals in any group retrieved pups. However, 12 h later, females that received bilateral OH-TAM implants into MPOA remained nonresponsive, while over 80% animals in other groups retrieved and gathered pups. The antiestrogen did not disrupt the display of postpartum maternal behavior in those females that were allowed to undergo normal parturition, but it significantly reduced the number of cesarean-delivered animals showing maternal behavior. Bilateral implants of OH-TAM into VMH, but not into MPOA, effectively blocked postpartum estrus. The MPOA implants of OH-TAM resulted in a significant reduction in cytoplasmic estrogen receptor levels and an increase in nuclear estrogen receptor concentrations. The results of these experiments lend support to the current hypothesis that estrogen acts most effectively in the MPOA to stimulate maternal behavior and in the VMH to facilitate sexual receptivity.

Animals↗

Maternal behavior and developmental psychopathology.

This paper reviews recent developments in the phenomenology, neurobiology, and genetics of maternal behavior in animal model systems from an evolutionary perspective on psychopathology. Following a review of the phenomenology and neurobiology of maternal behavior, recent studies addressing the role of genetic factors in the maternal behavior of rodents were identified in a search of literature in peer-reviewed journals. Gene knockout studies were evaluated with regard to mouse strain background, method of behavioral phenotyping, and quantification of the behavioral deficits. Gene knockout data were then analyzed using a cluster analysis technique. At least nine genes have been identified that are necessary for the expression of one or more aspects of maternal behavior. These genes encode for three transcription factors: three enzymes, including dopamine beta hydroxylase and neuronal nitric oxide synthase; two receptors, including the prolactin and the estrogen alpha receptor; and one neuropeptide, oxytocin. Cluster analysis suggested possible relationships between specific genes. Gene knockout technology has provided new insights into the molecular basis of maternal behavior that are congruent with the existing neurobiological literature. Future studies of genetic and environmental influences on maternal behavior have the potential to inform models of disease pathogenesis.

Animals↗

Lactogenic hormone regulation of maternal behavior.

Biological factors can profoundly affect a mother's response to her young. For example, it is well known that the hormones of pregnancy act on the maternal brain to stimulate the spontaneous onset of maternal behavior at parturition. Studies in the rat have provided an excellent model to investigate maternal behavior in mammals, since maternal behavior in rats is easily observable and readily quantifiable and it is well-documented that the endocrine state of gestation helps to bring about the onset of maternal behavior around the time of birth. The same response in virgin animals requires a number of days of constant exposure to pups before maternal-like behaviors emerge. To date, research has established that the steroid hormones, estradiol and progesterone, and the lactogenic hormones, prolactin and the placental lactogens, act in concert to stimulate maternal behavior in the pregnant female. Treatment of adult, virgin rats with these hormones can stimulate a rapid onset of maternal care. In the present chapter experiments are described that demonstrate key roles for prolactin and placental lactogens in the onset of maternal behavior. Central sites of action of prolactin and placental lactogens, including the medial preoptic area, appear to be involved in stimulating the onset of maternal care. Other studies are discussed which support the involvement of the prolactin receptor in the endocrine regulation of maternal behavior using prolactin receptor antagonist and 'knock-out' models in rats and mice, respectively. Overall, these studies indicate that during pregnancy the endocrine system primes the mother's brain so that the new mother displays appropriate and successful behaviors toward her newborn at parturition.

Animals↗

Evidence for the involvement of prolactin in the maternal behavior of the hamster.

The hormonal basis of maternal behavior in the hamster has not been clearly established. Treatment of parturient females on the day of delivery with the prolactin release inhibitor, bromocriptine, resulted in a significant disruption of maternal responsiveness at doses as low as 0.5 mg When pregnant females were implanted with ectopic pituitary grafts under the kidney capsule on day 8 or 9 of gestation to elevate circulating prolactin levels, there was no disruption of maternal behavior after bromocriptine injection on the day of delivery. Taken together, these data indicate that prolactin may be an important modulator of the natural onset of maternal behavior at parturition in the hamster.

Animals↗

Induction of maternal behavior in rats: effects of pseudopregnancy termination and placenta-smeared pups.

The onset of maternal behavior in Long-Evans rats was examined after pseudopregnancy (PsP) termination, both with and without exogenous estrogen administration, and in response to either clean or placenta-smeared stimulus pups. Natural (spontaneous) PsP termination was as effective in hastening the onset of maternal behavior as ovariectomy plus estrogen injection. If clean foster pups were presented as soon as pseudopregnancy terminated (first proestrus or cornified smear), maternal behavior was exhibited within 2 days; placenta-smeared foster pups presented at the same time elicited maternal behavior within 2 hr. The combination of initiating maternal-behavior testing immediately after the natural termination of pseudopregnancy and proffering placenta-smeared pups apparently simulates the hormonal milieu as well as the environmental cues present at parturition, noninvasively, producing optimal conditions for the rapid induction of maternal behavior.

Animals↗

Maternal behaviors associated with smothering: a preliminary descriptive study.

OBJECTIVES: To describe maternal behavior in 15 women identified as having smothered their children. DESIGN: A descriptive study of maternal behavior and interaction with her child, using videotapes of mother and child together. These were obtained by covert video surveillance in a hospital setting. Maternal behavior was rated using an assessment schedule designed to be used with video. RESULTS: The mothers showed a range of behaviors. Three groups emerged; one whose interaction with the child resembled normal maternal behavior, a second who interacted in a hostile way, and a third who showed a paucity of interaction. CONCLUSION: These preliminary data suggest that smothering may reflect more than one type of abnormal maternal relationship or attitude towards children. This may have implications for treatment and prognosis.

Adult↗

Maternal behavior in female C57BL/6J and DBA/2J inbred mice.

Inbred strains of mice exhibit different patterns of maternal behavior, providing material for studies of genetic influences on the expression of maternal behavior. Beginning 1 day after birth, maternal behavior was recorded daily for 14 days in the first and second litters of C57BL/6J (B6) and DBA/2J (D2) mothers. D2 mice had higher pup survival than B6 mice, and pup survival was higher in both strains in second litters than in first litters. D2 mothers spent more time engaged in maternal behavior, especially resting with, crouching over, and nursing pups than B6 mothers with first litters, but not with second litters. Not all measures of maternal behavior were correlated with pup survival; with both litters, B6 mothers retrieved pups faster than D2 mothers.

Analysis of Variance↗

Cocaine transiently impairs maternal behavior in the rat.

This paradigm distinguished between two hypotheses not previously directly addressed. Do repeated exposures to cocaine at critical times during pregnancy, when the neural mechanisms that support maternal behavior are being read, alter some fundamental neural underpinning of maternal behavior in rats? Alternatively, does cocaine alter maternal behavior only when circulating? During the 4 hr after cocaine injection (20 or 40 mg/kg), there were significant deficits in maternal behavior. In contrast, 16 hr after cocaine injection, drug-injected females, in which plasma cocaine had fallen to nondetectable levels, showed the normal maternal behavior of saline-injected controls. This pattern of impaired maternal behavior after cocaine injection, followed by normal behavior as blood levels returned to zero, was replicated over 8 days. It was concluded that cocaine impairs maternal behavior only when circulating and does not have a residual effect in the transiently drug-free, chronically drug-treated dam.

Aggression↗

Puerperal blockade of cholecystokinin (CCK1) receptors disrupts maternal behavior in lactating rats.

Blockade of cholecystokinin (CCK) receptors potentiates the morphine-induced disruption of maternal behavior. The present study was undertaken to determine whether treatment with lorglumide, a CCK1 antagonist during late pregnancy and early lactation can influence the maternal behavior during lactation. A possible influence of this treatment on general activity was also assessed. Twenty-seven female Wistar rats were pretreated with lorglumide (1.0mg/kg/day; sc) or saline for seven days, starting on the 17th d of pregnancy. After the withdrawal of this treatment, animals were acutely challenged with saline on day 5 and with morphine sulfate (3.0mg/kg; sc) on days 6,10, and 17 of lactation. Groups were pretreated with saline and challenged with saline (group SS) and morphine (group SM), pretreated with lorglumide and challenged with saline (group LS) and morphine (group LM). Animals were also tested for general activity on days 25 and 33 postpartum after an acute challenge with saline and morphine, respectively. Maternal behavior testing began 30 min after the acute injections at which time pups were placed throughout each mother's cage. Latencies for pup retrieval, grouping, crouching and for full maternal behavior responses were scored. Lorglumide pretreatment inhibited maternal behavior of LS vs SS group and potentiated the morphine-induced disruption of this behavior in all days of test (LM vs SM group). No significant differences were found in general activity on days 25 and 33 postpartum. These data suggest that blockade of CCK1 receptors during puerperal period has long-term implications for maternal behavior.

Animals↗

Involvement of the main but not the accessory olfactory system in maternal behavior of primiparous and multiparous ewes.

The respective roles of the main and accessory olfactory systems in the development of maternal behavior and selective suckling were investigated in parturient primiparous and multiparous ewes. Vomeronasal nerve section before parturition did not disturb either maternal behavior or maternal selectivity at suckling. By contrast, anosmia induced by zinc sulphate infusion had significant effects on the onset of maternal behavior in primiparous ewes. The onset of licking and of suckling were delayed and licking times and maternal bleats were reduced. Such disturbances were not observed in multiparous anosmic ewes, indicating that experience can compensate for the loss of olfactory information. On the other hand, anosmia prevented selective care regardless of maternal experience. Our results underline the importance of the main olfactory system for the development of adequate maternal behavior in sheep.

Animals↗