A potential gastrointestinal link between enhanced postnatal maternal care and reduced anxiety-like behavior in adolescent rats.

Early life experience impacts emotional development in the infant. In rat pups, repeated, brief (i.e., 15 min) maternal separation (MS15) during the first 1–2 postnatal weeks has been shown to increase active maternal care and to reduce later anxiety-like behavior in the offspring. We hypothesized that the anxiolytic effect of MS15 is partly due to increased intestinal release of cholecystokinin (CCK) in rat pups as a result of increased maternal contact. We predicted that rats with a history of MS15 would display less anxiety in the elevated plus maze (EPMZ) and novelty-suppressed feeding (NSF) tests, as compared with nonseparated (NS) controls, and that the anxiolytic effect of MS15 would be attenuated in rats in which daily MS15 was accompanied by systemic administration of a CCK-1 receptor antagonist (i.e., devazepide). Treatment groups included NS control litters, litters exposed to MS15 from postnatal days (P)1–10, inclusive, and litters exposed to MS15 with concurrent subcutaneous injection of devazepide or vehicle. Litters were undisturbed after P10 and were weaned on P21. Subsets of adolescent males from each litter were tested in the EPMZ on P40-41, while others were tested for NSF on P50-52. As predicted, rats with a developmental history of MS15 displayed reduced anxiety-like behavior in the EPMZ and NSF tests. The anxiolytic effect of MS15 was preserved in vehicle-treated rats, but was reversed in devazepide-treated rats. These results support the view that endogenous CCK-1 receptor signaling in infants is a potential pathway through which maternal-pup interactions regulate the development and functional organization of emotional circuits that control anxiety-like behavior in the offspring. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The duration of estradiol and progesterone exposure prior to progesterone withdrawal regulates oxytocin mRNA levels in the paraventricular nucleus of the rat

The nonapeptide oxytocin (OT) is important for milk ejection during lactation, uterine contractility at parturition, and the onset of maternal behavior. Sequential exposure to estradiol (E2) and progesterone (P) followed by P withdrawal increases OT mRNA in the paraventricular nucleus (PVN), and to a lesser degree the supraoptic nucleus (SON), of the rat 48 hours after the P is removed. Although increases in PVN OT mRNA are not accompanied by changes in posterior pituitary OT peptide content, the PVN contains OT neurons that project to both the posterior pituitary (magnocellular group) and extra pituitary sites (parvocellular groups). Steroid-induced increases in OT mRNA occur in both the magnocellular and the parvocellular regions of the PVN. The latter are believed to contribute to CNS release of OT which may be important for certain behaviors including the onset of maternal behavior. The same steroid sequence that increases PVN OT mRNA also induces maternal behavior in virgin ovariectomized rats. Exposure of animals to E2 and P for 2 weeks resulted in the shortest latency to the onset of maternal behavior in ovariectomized rats, whereas exposure for 6 days was associated with a longer latency. In this study we questioned if the duration of E2 and P exposure prior to P withdrawal is an important regulator of PVN OT mRNA levels. We compared OT mRNA levels in the PVN of virgin ovariectomized rats administered no steroid or sequential E2 and P for 2 weeks versus 6 days. On day 1 animals received steroid-filled or empty capsules followed by P-filled or empty capsules on day 3. In one steroid-treated group, E2 and P were continued for 6 days and in the other group for 14 days prior to P removal. Animals were sacrificed 48 hours after P removal. Levels of OT mRNA were compared among 6 day and 2 week steroid-treated animals and sham-treated animals. The relative abundance of OT mRNA was significantly increased, P < 0.05, in animals receiving the 2-week, but not the 6-day, steroid treatment compared to sham-treated animals. Pituitary OT peptide content was not significantly different among the three groups. We conclude that the duration of steroid exposure may be an important regulator of the level of OT mRNA in the PVN of the rat.     

Normal maternal behavior, but increased pup mortality, in conditional oxytocin receptor knockout females.

Oxytocin (Oxt) and the Oxt receptor (Oxtr) are implicated in the onset of maternal behavior in a variety of species. Recently, we developed two Oxtr knockout lines: a total body knockout (Oxtr–/–) and a conditional Oxtr knockout (OxtrFB/FB) in which the Oxtr is lacking only in regions of the forebrain, allowing knockout females to potentially nurse and care for their biological offspring. In the current study, we assessed maternal behavior of postpartum OxtrFB/FB females toward their own pups and maternal behavior of virgin Oxtr–/– females toward foster pups and compared knockouts of both lines to wildtype (Oxtr+/+) littermates. We found that both Oxtr–/– and OxtrFB/FB females appear to have largely normal maternal behaviors. However, with first litters, approximately 40% of the OxtrFB/FB knockout dams experienced high pup mortality, compared to fewer than 10% of the Oxtr+/+ dams. We then went on to test whether or not this phenotype occurred in subsequent litters or when the dams were exposed to an environmental disturbance. We found that regardless of the degree of external disturbance, OxtrFB/FB females lost more pups on their first and second litters compared to wildtype females. Possible reasons for higher pup mortality in OxtrFB/FB females are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of chronic and acute cocaine treatment on the onset of maternal behavior and aggression in Sprague-Dawley rats.

Pregnant rats (N?=?17) were treated either throughout gestation (Gestational Day 1–20) with 30 mg/kg per day (chronic cocaine) or with 1 15-mg/kg dose immediately following parturition (acute cocaine). Chronic and acute cocaine treatment delayed or diminished the postpartum onset of some components of maternal behavior, and chronically treated dams were significantly more aggressive toward a male intruder than acute cocaine-treated or saline-treated dams. Cocaine increased the latency to crouch over pups and decreased crouch duration during a 30-min observation period that immediately followed parturition. Latencies to nest build were also longer in more chronic cocaine-treated dams than in saline controls. On Day 6 postpartum, 83% of chronic cocaine-treated dams pinned and attacked an intruder male 8 or more times during a 10-min observation period, whereas only 4% of acute cocaine-treated and none of the saline-treated dams exhibited this much aggression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ontogeny of suckling in rats: Transitions toward adult ingestion.

Studied the suckling behavior of neonatal Sprague-Dawley rats on their own anesthetized mother from the day of birth until after weaning (35 days). Even newborn Ss were capable of nipple attachment without maternal assistance. Before 11–23 days of age, pups deprived of suckling for 22 hrs and nondeprived pups quickly attached to their mother's nipples, sucked, and remained attached to the nipple though no milk delivery occurred. Then behavior underwent at least 3 changes: (a) After 11–23 days of age, latency to attach became considerably elevated in nondeprived pups; (b) a 2nd change in latency occurred at 23–25 days of age, when nondeprived pups no longer even attached to the nipples of anesthetized mothers; and (c) about 14 days of age, deprived pups began to shift from 1 nipple to the next after initial attachment. These developmental changes were seen in other test situations in which pups were placed directly on a nipple and not required to search and when various periods of deprivation were utilized. These transitions were not critically dependent on the onset of visual function or on the pup's experience with food other than mother's milk. Suckling, therefore, in not an unmodified reflex but is an appetitive behavior that undergoes a series of changes during development. These transitions constitute major developmental events in the ontogeny of rat ingestive behavior. (48 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hypothermic vocalizations of rat pups (Rattus norvegicus) and direct maternal search behavior.

Emissions of ultrasonic vocalizations (USVs) by rat pups (Rattus norvegicus) during hypothermia have consequences for recovery and warming. The effects on dam behavior of USVs emitted by 3- to 11-day-old pups during hypothermia at rectal temperatures between 18 and 22°C was investigated Rat dams were tested in a Y maze with the home cage as a start box. Dams were given, in one condition, a choice between a hypothermic pup emitting USVs or a hypothermic, silent (anesthetized) pup and, in the other, a choice between 2 hypothermic, silent pups. Although differing in some acoustic properties from normal isolation calls, USVs emitted by hypothermic pups both elicited maternal search behavior and acted as directional cues for dams, in comparisons with control dams exposed only to silent pups. Thus USVs of pups recovering from extreme hypothermia have communicative as well as physiological significance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Retention of maternal behavior in nulliparous and primiparous rats: Effects of duration of previous maternal experience.

Lactating primiparous and nonlactating pup-induced maternal nulliparous female CD rats were given 1, 4, or 9 days of maternal experience with rat pups before they were isolated from the young. 25 days later, Ss were reexposed to 3–8 day old foster pups, and latencies to show maternal behavior in the home cage and a T-maze test were scored. In the home cage, the latencies of all nulliparous groups were shorter upon reinduction. Comparisons of primiparous and nulliparous groups revealed that primiparous females (1, 4, and 9 days combined) carried a pup, crouched, retrieved, and grouped the pups and built a good nest faster than did nulliparous females (combined groups). The number of behavioral differences between specific primiparous and nulliparous groups decreased as the length of prior maternal experience increased. In the T-maze, latencies to retrieve a pup were shorter in primiparous females. Results indicate that the processes underlying establishment of the long-term retention of short-latency maternal behavior in these groups may be comparable. (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Oxytocin activates the postpartum onset of rat maternal behavior in the ventral tegmental and medial preoptic areas.

Oxytocin binding (Bmax) was found to be higher in the ventral tegmental area (VTA) and the medial preoptic area (MPOA) at midparturition compared with Pregnancy Days 15–27 or Postpartum Days 5–7 in rat dams. Pup retrieval and assuming a nursing posture over pups were blocked in parturient dams by infusions of an oxytocin antagonist into the VTA or MPOA and by infusions of a vasopressin (V?) antagonist into the MPOA. These results implicate oxytocin in the VTA and MPOA and vasopressin in the MPOA, as well as a parturition-associated rise in oxytocin binding in these sites in the postpartum activation of maternal behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Arthralgias and cryoglobulinemia during protease inhibitor therapy in a patient infected with human immunodeficiency virus and hepatitis C virus

The effect of pre- and postnatal maternal dietary fatty acid composition on neurodevelopment in rat pups was studied. Timed pregnant dams were fed, beginning on d 2 of gestation and throughout lactation, either nonpurified diet (reference) or a purified diet whose fat source (22% of energy) was either corn oil or menhaden fish oil. On postnatal d 3, pups were randomly cross-fostered among dams of the same diet group and culled to 10 pups per dam. Milk was removed from stomachs of culled pups for fatty acid analyses. From postnatal d 4 to 30, pups were assessed daily for the appearance of neurodevelopmental reflexes. Auditory brainstem conduction times were measured on postnatal d 23 and 29. Pups were killed on postnatal d 30, and cerebrums were removed for fatty acid analyses. The fatty acid composition of maternal milk and pup cerebrums reflected maternal diet with higher levels of (n-3) and (n-6) fatty acids in the fish oil and corn oil groups, respectively. The time of appearance of auditory startle was significantly delayed (P = 0.004), and auditory brainstem conduction times on postnatal d 23 and 29 were significantly longer in pups of the fish oil- than corn oil-fed dams (P 相似文献   

Maternal responsiveness to infant Norway rat ( Rattus norvegicus) ultrasonic vocalizations during the maternal behavior cycle and after steroid and experiential induction regimens.

When removed from the nest and placed in a cool environment, Norway rat (Rattus norvegicus) pups emit ultrasonic vocalizations that can elicit maternal search behavior. The authors examined the behavior of pregnant dams, mothers, and virgin females during exposure to a pup that was either warm and silent or cool and vocalizing. Results indicate potentiated maternal reactions to a vocalizing pup: Mothers approached and maintained proximal orientation to a vocalizing pup far more than did virgin females. Elevated levels of proximal orientation appeared within hours of birth, increased during the 1st week postpartum, and declined by the time of weaning. Estrogen plus progesterone administration facilitated virgin females' proximal orientation toward vocalizing pups, whereas prolonged exposure to pups in the absence of hormones was without effect, suggesting that the ontogeny of the maternal response is regulated, at least in part, by maternal hormones. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mother-Infant Interactions in Rats Lacking CCKA Receptors.

Mediation of mother-infant interactions by the brain-gut peptide cholecystokinin (CCK) was examined by observing behavior of Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which lack functional CCKA receptors because of a genetic abnormality. OLETF (n = 10) and control (Long-Evans Tokushima Otsuka [LETO] n = 10) dams interacted with 1 pup of each line on Postpartum Days 6-9. OLETF pups received more body and anogenital licking and emitted substantially more ultrasonic vocalizations than LETO pups. OLETF dams carried pups less frequently and showed a nursing position more frequently than LETO dams. No significant Pup X Dam Line interactions or line differences in dams' activity were detected. The results provide convergent validity to previous pharmacological studies implicating CCK mediation of both infant and maternal behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Juvenile Rats Show Reduced c-fos Activity in Neural Sites Associated With Aversion to Pups and Inhibition of Maternal Behavior.

Juvenile rats (18-23 days old) interact avidly with pups as novel stimuli and show maternal behavior after only 1-3 days of pup exposure; adults initially avoid pups and require 3-9 days of pup exposure. Upon exposure to pups as novel stimuli, adults had more c-Fos-immunoreactive neurons in the hypothalamus and amygdala--regions associated with aversion to pups--than adults exposed to familiar pup stimuli (maternal) or not exposed to pups (p     

Hormonal interaction with stimulus situational factors in the initiation of maternal behavior in nonpregnant rats.

Previous hormonal studies have identified the hormonal and stimulus factors mediating the initiation of maternal behavior but have failed to reduce hormone-induced latencies of nonpregnant females to less than 1–2 days of continuous pup exposure. For the purpose of testing whether this delay is due to an olfactory-vomeronasal-mediated aversive reaction to pups like that found in untreated virgins, in 3 experiments estrogen-injected hysterectomized-ovariectomized (HO-EB) nonpregnant Charles River CD females were subjected to olfactory-vomeronasal deafferentation. Findings indicate that after HO-EB treatment, tendencies to initially avoid pup contact remain strong. Next, the hypothesis was explored that experiences during late pregnancy and/or parturition interact with hormonal priming to modify pup avoidance. Nonpregnant HO-EB females that had been exposed to pregnant-parturient females for 2 wks were tested under conditions simulating parturition. A high percentage rapidly initiated maternal behavior, but conditions during testing proved more important than prior exposure to pregnancy/parturition. Hormonally treated but not sham-treated females initiated maternal behavior most rapidly when first exposed to 1 newborn in the nest during the light phase. Prepartum caesarean-delivered females, however, responded maternally to 4 3–8 day old pups outside the nest, which indicates that additional factors operate at parturition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Experience-dependent cell survival in the maternal rat brain.

Postpartum maternal experience produces long-lasting changes in maternal behavior in the mother rat, which can be altered by early-life isolation. Postpartum experience also affects the regulation of adult neurogenesis in the neural circuit underlying maternal behavior, in a region-specific manner. Female rats were reared either with their mothers (MR) or in isolation in an artificial rearing (AR) paradigm. In adulthood, rats were mated and separated from their pups at birth. The following day, dams were injected with a mitotic marker and either allowed to interact with pups (maternal experience) or left alone. Results show that MR rats that acquire a later maternal experience show increases in cell survival in parts of the excitatory limb of the maternal neural network (bed nucleus of the stria terminalis and nucleus accumbens), but no changes in the inhibitory limb (amygdala). In comparison to AR inexperienced rats, AR maternally experienced rats show no increases in cell survival in the excitatory limb, but a striking reduction in cell survival in the inhibitory limb. The results suggest that early preweaning maternal isolation alters the structural plasticity that occurs following a postpartum maternal experience. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Day-by-day maturation of the long-term expression of cocaine sensitization acquired before weaning in the rat.

This study aimed to identify the ontogenetic period during which long-term expression of behavioral sensitization to cocaine begins to emerge. Rat pups aged 4, 8, 12, or 16 days received a pretreatment of 4 daily injections of 15 mg/kg sc: cocaine paired with the test chamber for 45 min. Pups were then tested for sensitization in that context after abstinence intervals ranging from 2 to 10 days. On test days, pups were videotaped, and their behavior was scored later. Sensitization was detected after intervals of 2, 4, 5, or 9 days in pups aged 4–7, 8–11, 12–15, or 16–19 days during pretreatment, respectively. These results suggest that the mechanisms for long-term retention of sensitization mature incrementally in the rat, starting to emerge gradually after the 1st week of age, whereas those relevant to short-term retention and initiation of sensitization are present earlier. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Litter gender composition affects maternal behavior of the primiparous mouse dam (Mus musculus).

Thirty-nine litters of the outbred Swiss CD-1 mouse strain were reduced at birth to 6 pups, according to three conditions MM (all males), MF (3 males and 3 females), or FF (all females). The maternal behavior of their respective dams (frequency and duration of nursing, licking, nestbuilding, and other activities such as eating, drinking, sniffing, grooming, and undirected locomotor activity) were scored during a single 10-min session on Days 2, 3, 5, 7, 10, 14, and 18. Dams rearing MM litters showed higher scores of maternal care on Days 2 and 18 in the case of nursing, on Days 2, 7, and 10 in the case of nest-building, and on Day 18 in the case of licking. These results confirm previous rat data, which indicated that male and female pups are exposed early in infancy to a different pattern of maternal behavior. Concomitant measurements of pup development (body-weight gain and achievement of a number of physiological and neurobehavioral landmarks) indicated that these effects of litter gender composition are not mediated by gross changes in the maturational trends of the pups. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparison of two positive reinforcing stimuli: Pups and cocaine throughout the postpartum period.

This set of experiments investigated the appetitive or motivational processes underlying the performance of maternal behavior. The place preference paradigm was adapted to simultaneously investigate the reinforcing properties of cocaine and pups for maternal, lactating dams. These modifications allowed the authors to assess which stimulus, either a 10 mg/kg sc injection of cocaine or 3 pups, had the strongest reinforcing value. At Postpartum Days 10 and 16, the dams preferred the cocaine cue-associated chamber, whereas the dams tested at Postpartum Day 8 preferred the pup cue-associated chamber. Overall, the data revealed an interaction between the postpartum period at testing and the exhibited preference for cocaine or pups. Further testing will investigate the neural circuitry underlying the appetitive processes of each stimulus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

An oxytocin antagonist infused into the central nucleus of the amygdala increases maternal aggressive behavior.

Decreased oxytocin levels in the amygdalas of rat dams following chronic gestational cocaine exposure have been correlated with heightened maternal aggressive behavior. In this experiment, drug-naive dams were implanted with bilateral cannulas into the central nucleus of the amygdala (CNA) or control area and infused with 1,000 or 500 ng of an oxytocin antagonist (OTA) or buffer, 4 hr before testing. Behavior was compared among dams infused with OTA into target areas just outside the CNA and cocaine-treated dams (infused with buffer). Dams infused with 1,000 ng OTA attacked intruders significantly more often than buffer-infused dams. OTA did not affect other behaviors, suggesting that disruption of oxytocin activity in the CNA may be sufficient to selectively alter maternal aggressive behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acute hunger of rat pups elicits increased kyphotic nursing and shorter intervals between nursing bouts: Implications for changes in nursing with time postpartum.

Earlier findings, based on limited behavioral observations, indicate that nursing behavior in rats declines dramatically in duration over time postpartum--despite increasing ingestion of milk by rat pups to meet their growth and metabolic needs--although hungry pups elicit more nursing than do well-nourished pups. The authors compared the nursing pattern in detail for 6 hr on Days 7 and 14 and induced hunger in pups acutely with mammary-duct-ligated dams unable to provide milk. Compared with Day 7, on Day 14, supine nursing and the interval between nursing bouts increased, whereas hovering over pups and kyphotic nursing decreased. When pups were increasingly hungry, these age-related changes were counteracted. Thus, the ingestive motivation of pups largely regulates the nursing pattern over time. (PsycINFO Database Record (c) 2010 APA, all rights reserved)