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Repeated morphine administration during pregnancy attenuates maternal behavior.

The present study tested the hypothesis that repeated administration of morphine on days 11-18 of pregnancy alters maternal behavior. Saline- and morphine-treated mothers were observed with their pups in two experiments. Rats were always tested twice a day during the light and dark phases of the reverse light/dark cycle. In Experiment 1, 12 types of activities and three types of nursing positions of mothers were recorded ten times during each 50-minute session for the 23-day lactation period. A decrease in nursing and active maternal behavior, and an increase in self-care, rearing and sniffing was found in morphine-treated mothers. Additionally, both saline- and morphine-treated mothers exhibited significantly more maternal behavior during the light, and non-maternal activities during the dark sessions of each day. Moreover, both saline- and morphine-treated mothers displayed significantly less maternal behavior and more non-maternal activities as postpartum time progressed. In Experiment 2, a different group of mothers was tested for pup retrieval from postnatal days 1 through 12. Morphine-treated mothers were slower than saline-treated mothers in retrieving all pups into the nest. However, there were no differences in latency to carry the first pup and return him/her to the nest. No unusual maternal behaviors were observed during the retrieval tests. Thus, the present study suggests that morphine administration during the second half of pregnancy attenuates some components of maternal behavior and increases non-maternal activities of mothers.

Animals↗

Mu 1 opioid receptor involvement in maternal behavior.

Previous studies have demonstrated that morphine inhibits the display of maternal behavior in lactating rats. Whether morphine exerts its actions specifically at the mu receptor has not yet been determined. The present study examined this possibility by evaluating whether naloxonazine, an irreversible and selective antagonist of the mu 1 opioid receptor subtype, is able to attenuate morphine's disruptive effect on maternal behavior in primiparous lactating rats. Experiment 1 compared the ability of naloxonazine (AZINE) and naloxone (NAL) to block the action of morphine (MOR) on maternal care. Virgin, Sprague-Dawley rats were mated in our colony and on day 3 postpartum (parturition, day 0) all rats received jugular catheters. On day 6 the mothers received one of the following treatments: MOR alone (10 mg/kg, SC, N = 10); MOR (10 mg/kg, SC) 24 hr after AZINE pretreatment (10 mg/kg, IV, N = 10); MOR (10 mg/kg, SC) 24 hr after NAL pretreatment (10 mg/kg, IV, N = 8); or MOR (10 mg/kg, SC) immediately after NAL (0.5 mg/kg, SC, N = 10). MOR alone completely disrupted maternal behavior (0% responded) which was blocked by prior NAL administration (100%). AZINE pretreatment 24 hr earlier partially blocked MOR disruption of MB (40% responded; significantly different from MOR alone). The response of rats pretreated 24 hr earlier with NAL did not differ from MOR alone. AZINE blocked MOR's effect on pup retrieval to an even greater degree (70% responded vs. 10% in MOR alone). Experiment 2 determined the ability of AZINE to interfere with varying doses of MOR on maternal behavior.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Oxytocin antiserum delays onset of ovarian steroid-induced maternal behavior.

We have previously reported that intracerebroventricular (ICV) administration of oxytocin (OXY) produces a significant increase in maternal behavior in ovariectomized (OVXed) rats given a single priming dose of estrogen. Arginine vasopressin (AVP) has a weaker and more delayed but significant facilitating effect on the onset of maternal behavior. Other investigators have demonstrated that prolonged treatment of OVXed nulliparous rats with estrogen and progesterone followed by withdrawal of progesterone shortens the latency of onset of maternal behavior. We hypothesized that ovarian steroids increase the onset of maternal behavior by a central mechanism involving OXY and possibly AVP. To test this nulliparous Sprague Dawley rats were given SC one Silastic capsule containing 4.4 mg of 17 beta-estradiol eight days after OVX and three capsules each containing 40 mg of progesterone ten days after OVX. Progesterone capsules were removed on the 20th day after OVX, 24 hrs before the introduction of three rat pups (1-5 days old). One hr prior to introduction of pups animals received ICV 10 microliters of anti-oxytocin antiserum (AOA), anti-arginine vasopressin antiserum (AVA), anti-neurotensin antiserum (ANA), normal rabbit serum (NRS), AOA + 250 ng OXY or no ICV infusion. Animals receiving AOA displayed significantly less maternal behavior compared to animals receiving NRS, ANA or no ICV infusion over the first two, six and 25 hrs of pup contact. OXY significantly reversed the inhibitory effect of AOA in the first two hrs of pup contact. AVA significantly decreased the onset of maternal behavior compared to ANA or no ICV infusion over the first six hrs of pup contact.

Animals↗

Disinhibition of maternal behavior following neurotoxic lesions of the hypothalamus in primigravid rats.

Virgin female rats do not respond maternally to foster pups due to an endogenous neural circuit that actively inhibits the display of maternal behavior. Once pregnant, primigravid rats will continue to avoid foster pups until just prior to or at parturition. Anosmia or lesions of the olfactory tract, medial amygdala, and areas of the hypothalamus will stimulate virgin females to display maternal behavior rapidly, but little is known of the effect of these lesions in primigravid rats. The objective of the present study was to determine if neurotoxic lesions of the dorsomedial (DMH) and ventromedial nuclei (VMH) of the hypothalamus will advance the onset of maternal behavior in primigravid rats. Nulliparous Sprague-Dawley female rats were mated and then on day 8 of gestation bilaterally infused with N-methyl-d-aspartic acid (NMDA; 8 microg/0.2 microl/side) or vehicle directed toward either the DMH or VMH. Beginning on day 15 of gestation until parturition, females were tested daily for maternal responsiveness. DMH and VMH lesions significantly advanced the onset of maternal behavior (5-6 days vs. 0-1 day before parturition) in first-time pregnant rats. These results indicate that the DMH and VMH are involved in the regulation of maternal behavior and may be part of an endogenous neural circuit that inhibits maternal behavior during pregnancy.

Animals↗

The habenular complex mediates hormonal stimulation of maternal behavior in rats.

The role of the habenular complex (Hbc) in the hormonal onset and nonhormonal maintenance of maternal behavior in rats was examined. In Experiment 1, bilateral lesions were produced in the Hbc on Gestational Day (GD) 12. On GD 16, animals were hysterectomized-ovariectomized and given estradiol benzoate (EB); they were then tested for maternal behavior 48 hr later. Hbc lesions delayed the appearance of all components of maternal behavior for several days. In Experiment 2, large Hbc lesions that were produced on Postpartum Day 4 caused only 1- or 2-day deficits in maternal behavior. These data suggest that the Hbc mediates the hormonal onset of maternal behavior. During the postpartum period, however, the importance of the Hbc for maternal behavior diminishes as the hormones of pregnancy become less important.

Animals↗

Medial preoptic area interactions with the nucleus accumbens-ventral pallidum circuit and maternal behavior in rats.

Several experiments explored the roles of nucleus accumbens (NA), ventral pallidum (VP) and medial preoptic area (MPOA) in the regulation of maternal behavior in rats. A preliminary experiment found that bilateral radiofrequency lesions of medial NA did not disrupt maternal behavior. Experiment 1 found that bilateral infusions of muscimol into VP, but not into medial NA, reversibly disrupted maternal behavior. Experiment 2 found that unilateral muscimol injections into VP disrupted maternal behavior to a greater extent when paired with a contralateral N-methyl-d-aspartic acid (NMDA) MPOA lesion than when paired with a sham MPOA lesion. Experiment 3 showed that a unilateral NMDA MPOA lesion paired with a contralateral NMDA VP lesion (Contra group) disrupted maternal behavior to a much greater extent than did sham NMLA lesions or NMDA lesions of MPOA and VP ipsilateral to one another. Experiment 3 focused on the specificity of the maternal behavior disruptions and found that the primary maternal deficit in the Contra females was a severe deficit in retrieval behavior. Importantly, these females showed normal hoarding behavior, home cage activity, and elevated plus maze activity. Experiment 3 used Neu N immunohistochemistry to define the extent of MPOA and VP excitotoxic lesions. It is hypothesized that MPOA acts to facilitate the active components of maternal behavior by inhibiting NA, which then releases VP from GABAergic inhibition, and such disinhibition of VP allows pup stimuli to trigger appropriate maternal responses.

Analysis of Variance↗

Expression of intracellular progesterone receptors in rat brain during different reproductive states, and involvement in maternal behavior.

Progesterone is one of a complex of hormones which influences the occurrence of maternal behavior in rats. The present study provides information on progesterone's mechanism and possible neural site(s) of action with respect to maternal responsiveness. Progesterone can exert cellular effects by acting on membrane receptors or by acting on intracellular receptors. In the first experiment we show that RU 486 can antagonize progesterone's inhibitory effect on maternal behavior. Since RU 486 acts as an antagonist to progesterone's action at its intracellular receptor, these results support the involvement of that receptor in maternal behavior control. The second experiment employs immunocytochemical techniques to detect the number of cells in various forebrain regions which contain intracellular progesterone receptors during different reproductive states. The number of cells which contained progesterone receptors was higher toward the end of pregnancy (progesterone is presumably exerting its effects on maternal behavior at this time) when compared to either early pregnancy or lactation in the following forebrain regions: anteroventral periventricular nucleus of the preoptic area; medial preoptic area; ventral part of the bed nucleus of stria terminalis; ventrolateral division of the ventromedial nucleus; arcuate nucleus; anterior paraventricular nucleus of the hypothalamus; and medial amygdala. The possible involvement of these regions as a site or sites where progesterone might exert its effects on maternal behavior is discussed.

Analysis of Variance↗

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.

Adrenergic Agents↗

The effects of adrenalectomy and corticosterone replacement on maternal behavior in the postpartum rat.

It is well known that the hypothalamic-pituitary-adrenal (HPA) axis is activated during stress. Recent work suggests it is also implicated in the regulation of "normal" behaviors. The present studies investigated the effects of adrenalectomy and of varying glucocorticoid concentrations on adult maternal behavior in primiparous rats. In two studies, rats in late pregnancy were adrenalectomized or given sham surgeries and were tested for maternal behavior. In the first study, primiparous rats were given 0, 25, 100, 300, or 500 microg/ml of corticosterone in their drinking water. In the second study, primiparous rats were given either control or corticosterone time-release pellets. Blood samples were taken to ensure that rats demonstrated levels of corticosterone in blood that were relative to doses received. In studies one and two, primiparous adrenalectomized rats showed slightly, but significantly, lower levels of some maternal behaviors, including licking and time in nest, than primiparous sham rats. Primiparous rats given higher doses of corticosterone replacement showed higher levels of these maternal behaviors than primiparous rats given lower doses of corticosterone. In conclusion, adrenalectomy decreases, but does not abolish, maternal behavior. Corticosterone replacement reverses these effects. Corticosterone is not necessary for the initiation or maintenance of maternal behavior but plays a role in the modulation of ongoing maternal behavior.

Administration, Oral↗

A dose-response study of chronic cocaine on maternal behavior in rats.

To determine if there was a dose-response relationship with regard to cocaine treatment and maternal behavior exhibited by lactating rats at doses that had not been previously investigated, we examined the effects of three doses of chronic cocaine administration throughout gestation on both onset and established maternal behavior. Dams were injected (SC) with 6.3, 13, or 25 mg/kg cocaine HCl or an equivalent volume of saline throughout gestation; maternal behavior was tested on postpartum days 1 and 3. At the doses employed, cocaine disrupted the onset of only one pup-directed component of maternal behavior significantly in a dose-response manner, although there were several statistically nonsignificant dose-dependent trends of behavioral disruptions. No pup-directed behaviors were disrupted during testing for established maternal behavior. These results indicate that gestational cocaine treatment at doses of 25 mg/kg and less have only minimal effects on the onset and no effect on the maintenance of maternal behavior using our paradigm. The relationship of the present findings to previous work is discussed.

Animals↗

Maternal and littermate deprivation disrupts maternal behavior and social-learning of food preference in adulthood: tactile stimulation, nest odor, and social rearing prevent these effects.

Maternal and littermate (social) separation, through artificial rearing (AR), disrupts the development of subsequent maternal behavior and social learning in rats. The addition of maternal-licking-like stimulation during AR, partially reverses some of these effects. However, little is know about the role of social stimuli from littermates and nest odors during the preweaning period, in the development of the adult maternal behavior and social learning. The purpose of this study was to examine the effects of peer- and peer-and-odor rearing on the development of maternal behavior and social learning in rats. Female pups were reared with mothers (mother reared-MR) or without mothers (AR) from postnatal day (PND) 3. AR rats received three different treatments: (1) AR-CONTROL group received minimal tactile stimulation, (2) AR-ODOR females received exposure to maternal nest material inside the AR-isolation-cup environment, (3) AR-SOCIAL group was reared in the cup with maternal nest material and a conspecific of the same-age and same-sex and received additional tactile stimulation. MR females were reared by their mothers in the nest and with conspecifics. In adulthood, rats were tested for maternal behavior towards their own pups and in a social learning task. Results confirm our previous report that AR impairs performance of maternal behavior and the development of a social food preference. Furthermore, social cues from a littermate, in combination with tactile stimulation and the nest odor, reversed the negative effects of complete isolation (AR-CONTROL) on some of the above behaviors. Exposure to the odor alone also had effects on some of these olfactory-mediated behaviors. These studies indicate that social stimulation from littermates during the preweaning period, in combination with odor from the nest and tactile stimulation, contributes to the development of affiliative behaviors.

Age Factors↗

Reproductive success, postpartum maternal behavior, and masculine sexual behavior of neonatally androgenized female hamsters.

Sex differences in maternal behavior induced by pup stimulation (sensitization) have been reported for rats and hamsters and may be affected by the presence or absence of perinatal androgen treatment. Postpartum maternal behavior and litter survival in golden hamsters treated with testosterone propionate (TP) as neonates were studied. A high dose of TP (300 micrograms)1 eliminated feminine reproductive capacity when given on Day 2 or 4 postpartum and had no discernible effect on Day 12. Treatment on Days 6, 8, or 10 resulted in treatment day-dependent deficiencies in reproductive success which fell short of sterility in most females. These deficiencies included low birth weight, weight gain, and higher litter losses than controls. However, the maternal behavior of TP dams, as measured by retrieval and crouching, appeared to be normal. The disparity between delivery and successful rearing of normal-weight young may include uterine incompetence, lactation deficiency, and hypercannibalism. Behavioral masculinization was a more sensitive index of neonatal androgen action than any aspect of defeminization, but the two phenomena were dissociated in individuals.

Animals↗

Induction of brain prolactin receptor long-form mRNA expression and maternal behavior in pup-contacted male rats: promotion by prolactin administration and suppression by female contact.

Prolactin (PRL) is considered to induce maternal behavior toward foster young in female rats. In the present study, we studied the relationship between pup contact-induced maternal behavior and serum PRL concentrations and brain PRL receptor (PRL-R) mRNA expression in male rats. Both intact and castrated male rats exposed to foster pups gradually developed caretaking behavior such as crouching and licking, but their exhibitions of other maternal behavior components, retrieval/grouping and nest building, were incomplete. However, in the male rats displaying crouching and licking, the concomitant increases in serum PRL concentration and brain mRNA expression for long-form PRL-R were observed. The expression of short-form PRL-R mRNA in the brain was not stimulated by pup contact. Administration of PRL remarkably promoted the onset of those maternal responses in male rats. On the other hand, when an intact male rat was housed in a cage where a lactating female rat and her pups were living, his scores in maternal behavior tests toward pups were lowered. And, concomitantly, increases in serum PRL concentration and brain expression of long-form PRL-R mRNA were reduced. In castrated male rats, however, the ratings of maternal behavior toward foster young, serum PRL concentration increase, or brain long-form PRL-R mRNA expression were not reduced at all by cohabitation with a female and her pups. These findings indicated that maternal behavior was triggered and maintained in pup-contacted male rats through elevated serum PRL levels and induced brain long-form PRL-R.

Animals↗

Dorsolateral connections of the medial preoptic area and maternal behavior in rats.

The lateral connections of the medial preoptic area (MPOA) are essential for maternal behavior in rats. The purpose of this study was to more exactly specify the nature of this pathway. Experiment 1 found that knife cuts that severed the dorsolateral connections of the MPOA were as effective as complete cuts in disrupting maternal behavior, whereas knife cuts that severed the ventrolateral MPOA connections were ineffective. These results suggest that MPOA efferents and afferents critical for maternal behavior leave or enter the MPOA dorsolaterally. Experiment 2 located possible sources of critical afferent input. Lactating rats received MPOA lateral cuts with a horseradish peroxidase (HRP)-coated wire knife. Full lateral cuts and dorsolateral cuts disrupted maternal behavior and labeled more cells with HRP in the nucleus of the solitary tract and the locus coeruleus than did ventrolateral cuts, which did not disrupt maternal behavior.

Animals↗

The effects of cocaine on maternal behaviors in the rat.

Although recent research has focused on the behavioral teratology of cocaine, there has been little attention centered on the effects of cocaine use on parenting behaviors after birth. This experiment investigated the effects of cocaine on parental (generally termed maternal) behavior in the rat. Four types of adult rats were tested for these effects over a 10-day testing period: lactating primiparous female dams, primiparous females, nulliparous females, and males. Subjects were injected daily with cocaine (5 mg/kg) or saline. Ten minutes postinjection each subject was placed in a cage with three stimulus pups and nesting material, and observed for several measures of maternal behavior for 5 minutes, including sniffing, licking, and retrieving pups. Subjects were also rated on a maternal behavior scale at 60 minutes and 24 hours postinjection, and on nest quality. Cocaine reduced both the total number and duration of sniffing and licking maternal behaviors, and resulted in a lower maternal behavior rating at 60 minutes compared to saline-treated subjects. Among those subjects that retrieved pups within the first 5 minutes, cocaine-injected subjects retrieved for a longer duration. These results also suggest impaired maternal behavior, since rapid retrievals would have been more efficient in maintaining a nest huddle. Thus, cocaine impaired the parenting ability of both male and female rats, with and without previous parenting experience.

Animals↗

[Patterns of maternal behavior of rats genetically selected for opposite coping styles].

Maternal behavior of Koltushi High- and Low-avoidance (KHA and KLA) rats strains was assessed over the prewealing period (days 6-21). Ten litters of each strain were observed during the light phase of the light/dark cycle. In a series of experiments, rat pups were taken from the maternal nest and placed into the opposite corner of the cage. The following parameters of the maternal behavior were recorded: the latency of the first contact with the pups, pup licking, latency of carrying/retrieval of the first pup back to the nest, time of returning to the nest of the whole litter, and mother's spontaneous behavior (grooming and locomotion time) over the course of 10 min of observation. KLA mothers stayed with their pups and took care of them more frequently than KHA mothers during the light phase of the circadian cycle. Time of self-grooming was significantly higher in KHA rats. The highest levels of self-grooming of mothers was registered on the first day of testing. The latency of the first coming to pups after their removal from the nest was lower in KHA rats, but they needed more time to returned all pups to the nest. The experimental evidence suggests that the KHA but not KLA rats with the active coping style and higher stress reactivity display disorders in maternal behavior in a novel situation.

Adaptation, Psychological↗

Neural basis of maternal behavior in the rat.

This article presents a review of the neural and neurochemical regulation of maternal behavior in the rat, emphasizing the role of the medial preoptic area (MPOA) and its neural connections in this regulation. Evidence for the role of the MPOA includes the following and will be discussed: (1) Axon-sparing lesions of the MPOA disrupt maternal behavior, indicating the involvement of MPOA neurons rather than fibers of passage. (2) Estradiol acts on the MPOA to facilitate maternal behavior. (3) An MPOA-to-lateral preoptic area-to-ventral tegmental area circuit may be part of the output pathway by which the MPOA influences maternal behavior. (4) MPOA neural circuitry may interact with olfactory neural circuitry and with the motor system to influence maternal responsiveness. (5) Opioid neural pathways appear to inhibit, and oxytocinergic neural pathways appear to promote, maternal behavior.

Animals↗

First and second order maternal behavior related afferents of the lateral habenula.

We demonstrated previously that the lateral habenula (Lhb) mediates maternal behavior. Our present goal was to identify the first and second order afferent connections of the Lhb, particularly those relevant for maternal behavior. Using pseudorabies virus (PRV) as a retrograde transneuronal tracer and the retrograde tracer Fluoro-Gold, we identified first order Lhb afferent projections from the lateral preoptic area, bed nucleus of the stria terminalis, nucleus accumbens and ventral tegmental area, each important for the display of maternal behavior. Maternally relevant second order neurons originated from the medial preoptic area and amygdala. Additional regions with first and second order neurons afferent to the Lhb were also identified.

Afferent Pathways↗