Estradiol receptor-alpha expression in hypothalamic and limbic regions of ewes is influenced by physiological state and maternal experience

The influence of estrus, pregnancy, parturition, and maternal experience on the expression of estrogen receptor-alpha (ERalpha) was investigated in hypothalamic and limbic regions of the sheep brain, using immunocytochemistry. Four days before parturition, previous maternal experience was associated with a higher density of ERalpha-labeled neurons in the paraventricular and supraoptic nuclei, the medial preoptic area, and the medial amygdala, but not in the mediobasal hypothalamus. Furthermore, an interaction was found between physiological state and experience in the peripartum period as the effect of experience existing 4 days prepartum was not found at parturition, when densities were lowest both in primiparous and in multiparous ewes. An additional effect of physiological state was also observed between parturition and estrus, densities being significantly lower at parturition than at estrus in the SON, PVN, and MPOA, but not in the medial amygdala. These results indicate that in sheep ERalpha expression is influenced by previous physiological and/or maternal experience at specific times of the reproductive cycle. They are also congruent with the higher ability of multiparous than nulliparous ewes to show maternal behavior several days prepartum.     

Loss of calcineurin from the medial preoptic area of primiparous rats

Western blot analyses reveal that calcineurin A (CNA), which is present in the hippocampus, basolateral amygdala, parietal cortex, and MPOA of virgin males and females, is undetectable only in the MPOA of primiparous females regardless of whether they had postpartum pup contact or not. In contrast, CNB was expressed at unchanging levels in the PC and MPOA. Similarly, G(alphao) and PKA(RI) were expressed at high levels in all of the brain regions of virgin males, virgin females, and primiparous females, supporting the concept that this loss of CNA is a specific event. Understanding how and why the expression of CNA, the sole neuronal Ca2+/CaM-dependent protein phosphatase, is down-regulated specifically in the MPOA of primiparous females may yield some insight into the signal transduction events that mediate the onset of mammalian maternal behavior.     

Preventing physical interactions between parturient ewes and their neonate differentially impairs the development of maternal responsiveness and selectivity depending on maternal experience

The present study investigated whether deprivation of nursing or of any physical interaction with the lamb impairs the onset of maternal responsiveness and the establishment of selectivity in primiparous and multiparous ewes. Just after parturition, ewes could interact freely with their lamb, or could only lick their lamb but not nurse them, or could neither lick nor nurse them for the first 4 h. At 4 h, mothers were successively observed for 3 min with an alien lamb and then with their own lamb. Only 5/14 primiparous mothers accepted their own lamb following deprivation of all physical contact whereas all multiparous mothers did so (19/19). Also, deprivation of all physical contact resulted in a significantly higher proportion of multiparous mothers accepting an alien lamb (6/18) than following deprivation of nursing only (0/19) indicating an impairment in selectivity. Finally, there was no indication that preventing only nursing led to a deficit either in maternal responsiveness or selectivity, neither in primiparous nor in multiparous ewes. These findings underline the importance of perception of olfactory cues from amniotic fluids through licking and/or physical contact and interacting with the lamb for the development of maternal responsiveness and selectivity.     

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.     

Prepartum plasma estradiol and postpartum cortisol, but not oxytocin, are associated with interindividual and breed differences in the expression of maternal behaviour in sheep

Consistent, individual differences in the expression of maternal behaviour have been described in several species including the sheep. The neuroendocrine mechanisms underlying the onset of maternal behaviour in the sheep have been described, although the relationship between hormonal events and individual differences in behaviour has yet to be determined. In this study, we examined whether the individual differences in plasma estradiol, progesterone, oxytocin and cortisol concentrations were related to observed individual and breed differences in maternal behaviours in two breeds of sheep (Scottish Blackface and Suffolk) known to differ in maternal behavioural expression. Maternal estradiol concentration increased rapidly before parturition and was higher in Blackface ewes than Suffolk ewes. Plasma progesterone declined before parturition and was higher in Suffolk than Blackface ewes. Prepartum estradiol, but not progesterone, was related to individual differences in maternal grooming of the lamb. Plasma oxytocin did not differ between breeds in late gestation. There was a tendency for oxytocin to be higher in Blackface than Suffolk ewes immediately after birth. However, there were no significant relationships between prepartum or postpartum oxytocin and any maternal behaviours. Plasma cortisol was higher in Blackface than Suffolk ewes in the last days of pregnancy but rose in both breeds over the last 24 h before parturition and did not differ at delivery. Cortisol peripartum was negatively related to individual differences in maternal affiliative behaviours. These data suggest that estradiol, and potentially cortisol, may mediate individual differences in maternal behaviour in sheep.     

The effect of experience on twin-care in New Zealand Romney sheep

Behaviour of ewes at lambing was observed in a flock of N.Z. Romney sheep composed of selected (or “elite”) ewes that had produced litters of 2 or more lambs at least twice previously, and 2-year-old ewes that had produced 0, 1 or 2 lambs at 12 months of age. The observations concentrated on twin-bearing ewes.Only 6% of twin-bearing elite ewes became separated from a twin compared with 16% of primiparous ewes. Conflicts between elite and younger ewes over ownership of twin lambs were won by elite ewes in 6 of 7 cases, and elite ewes gathered their twin lambs together more quickly after artificial separation than primiparous ewes.Irrespective of litter size, primiparous ewes remained within 20 m of their birth-site for a mean of 11 h compared with 7 h for elite ewes, and the incidence of separation from a twin in primiparous ewes was higher with ewes that moved from the birth-site within 6 h of birth than in those that remained for more than 6 h. Also, primiparous ewes appeared more reluctant than elite ewes to leave one twin to recover the other that had been deliberately separated.The behaviour towards twins in the small number of 2-year-old ewes that had produced twins at 12 months of age was similar to that of the elite ewes in several respects, but contrasted with behaviour of primiparous mothers of the same age. This indicates that twin care improved with experience rather than age. The behaviour towards twins in 2-year-old ewes that had previously produced a single only tended to fall between that of primiparous ewes and ewes that had produced twins when 12 months old.     

Dissociated functional pathways for appetitive and consummatory reproductive behaviors in male Syrian hamsters

In many species, including Syrian hamsters, the generation of male reproductive behavior depends critically on the perception of female odor cues from conspecifics in the environment. The behavioral response to these odors is mediated by a network of steroid-sensitive ventral forebrain nuclei including the medial amygdala (MA), posterior bed nucleus of the stria terminalis (BNST) and medial preoptic area (MPOA). Previous studies have demonstrated that each of these three nuclei is required for appropriate sexual behavior and that MA preferentially sends female odor information directly to BNST and MPOA. It is unknown, however, how the functional connections between MA and BNST and/or MPOA are organized to generate different aspects of reproductive behavior. Therefore, the following experiments used the asymmetrical pathway lesion technique to test the role of the functional connections between MA and BNST and/or MPOA in odor preference and copulatory behaviors. Lesions that functionally disconnected MA from MPOA eliminated copulatory behavior but did not affect odor preference. In contrast, lesions that functionally disconnected MA from BNST eliminated preference for volatile female odors but did not affect preference for directly contacted odors or copulatory behavior. These results therefore demonstrate a double dissociation in the functional connections required for attraction to volatile sexual odors and copulation and, more broadly, suggest that appetitive and consummatory reproductive behaviors are mediated by distinct neural pathways.     

Pen size and parity effects on maternal behaviour of Small-Tail Han sheep

The aim of this experiment was to study the effects of pen size and parity on maternal behaviour of twin-bearing Small-Tail Han ewes. A total of 24 ewes were allocated to a 2×2 design (six per pen), with parity (primiparous or multiparous) and pen size (large: 6.0×3.0 m; small: 6.0×1.5 m) as main effects at Linyi University, Shandong Province, China. Behaviour was observed from after parturition until weaning. All ewes were observed for 6 h every 5 days from 0700 to1000 h and from 1400 to 1700 h. Continuous focal animal sampling was used to quantify the duration of maternal behaviours: sucking, grooming and following as well as the frequency of udder accepting, udder refusing and low-pitched bleating. Oestradiol and cortisol concentrations in the faeces (collected in the morning every 5 days) were detected using EIA kits. All lambs were weighed 24 h after parturition and again at weaning at 35 days of age. The small pen size significantly reduced following (P<0.005), grooming (P<0.001) and suckling durations (P<0.05), as well as the frequency of udder refusals (P<0.001). However, there was a significant interaction with ewe parity, with decreased grooming and suckling in the small pen largely seen in the multiparous ewes (P<0.001). Independent of pen size, multiparous ewes accepted more sucking attempts by their lambs (P<0.05) and made more low-pitched bleats than primiparous ewes (P<0.001). Multiparous ewes had higher faecal oestradiol concentrations than primiparous ewes (P<0.001), and ewes in small pens had higher faecal cortisol levels compared with ewes in larger pens (P<0.001). As lambs increased in age, the duration of maternal grooming, following and suckling as well as frequency of udder acceptance and low-pitched bleating all declined, and the frequency of udder refusing increased (P<0.001 for all). Ewe parity, but not pen size, affected lamb weight gain during the period of observation (P<0.001). This is the first study to show that pen size, interacting with parity, can affect the expression of maternal behaviour in sheep during lactation. The study is also the first to report on the maternal behaviour of Chinese native sheep breeds (Small-Tail Han sheep), with implications for the production of sheep in China.     

Endogenous oxytocin is necessary for preferential Fos expression to male odors in the bed nucleus of the stria terminalis in female Syrian hamsters

Successful reproduction in mammals depends on proceptive or solicitational behaviors that enhance the probability of encountering potential mates. In female Syrian hamsters, one such behavior is vaginal scent marking. Recent evidence suggests that the neuropeptide oxytocin (OT) may be critical for regulating this behavior. Blockade of OT receptors in the bed nucleus of the stria terminalis (BNST) or the medial preoptic area (MPOA) decreases vaginal marking responses to male odors; lesion data suggest that BNST, rather than MPOA, mediates this effect. However, how OT interacts with sexual odor processing to drive preferential solicitation is not known. To address this issue, intact female Syrian hamsters were exposed to male or female odors and their brains processed for immunohistochemistry for Fos, a marker of recent neuronal activation, and OT. Additional females were injected intracerebroventricularly (ICV) with an oxytocin receptor antagonist (OTA) or vehicle, and then tested for vaginal marking and Fos responses to sexual odors. Colocalization of OT and Fos in the paraventricular nucleus of the hypothalamus was unchanged following exposure to male odors, but decreased following exposure to female odors. Following injections of OTA, Fos expression to male odors was decreased in BNST, but not in MPOA or the medial amygdala (MA). Fos expression in BNST may be functionally relevant for vaginal marking, given that there was a positive correlation between Fos expression and vaginal marking for BNST, but not MPOA or MA. Together, these data suggest that OT facilitation of neuronal activity in BNST underlies the facilitative effects of OT on solicitational responses to male odors.     

Brain CRF-binding protein modulates aspects of maternal behavior under stressful conditions and supports a hypo-anxious state in lactating rats

Reduced corticotropin-releasing factor (CRF) receptor activation in the postpartum period is essential for adequate maternal behavior. One of the factors contributing to this hypo-activity might be the CRF-binding protein (CRF-BP), which likely reduces the availability of free extracellular CRF/urocortin 1. Here, we investigated behavioral effects of acute CRF-BP inhibition using 5 μg of CRF_(6-33) administered either centrally or locally within different parts of the bed nucleus of the stria terminalis (BNST) in lactating rats. Additionally, we assessed CRF-BP expression in the BNST comparing virgin and lactating rats.Central CRF-BP inhibition increased maternal aggression during maternal defense but did not affect maternal care or anxiety-related behavior. CRF-BP inhibition in the medial-posterior BNST had no effect on maternal care under non-stress conditions but impaired the reinstatement of maternal care following stressor exposure. Furthermore, maternal aggression, particularly threat behavior, and anxiety-related behavior were elevated by CRF-BP inhibition in the medial-posterior BNST. In the anterior–dorsal BNST, CRF-BP inhibition increased only non-maternal behaviors following stress. Finally, CRF-BP expression was higher in the anterior compared to the posterior BNST but was not different between virgin and lactating rats in either region.Our study demonstrates a key role of the CRF-BP, particularly within the BNST, in modulating CRF's impact on maternal behavior. The CRF-BP is important for the reinstatement of maternal care after stress, for modulating threat behavior during an aggressive encounter and for maintaining a hypo-anxious state during lactation. Thus, the CRF-BP likely contributes to the postpartum-associated down-regulation of the CRF system in a brain region-dependent manner.     

Upregulation of astrocytic basic fibroblast growth factor in the cingulate cortex of lactating rats: time course and role of suckling stimulation

Previous work from our laboratory has shown that there is a much higher level of bFGF and GFAP immunoreactivity in area 2 of the cingulate cortex (Cg2) of rats on day 16 of lactation than in cycling or late pregnant females. To examine the time course of this change, in the first of the current studies, we compared bFGF and GFAP immunoreactivity in the brains of lactating females on postpartum day 4 (PP4), day 10 (PP10), day 16 (PP16), and day 24 (PP24) with that of cycling and ovariectomized (OVX) females. In the second study, we investigated whether the maintenance of these changes in bFGF and GFAP depended on suckling stimulation by removing litters on day 1 or day 16 postpartum and examining the brains of the dams on day 4 (Pr4) or day 24 (Pr24) postpartum, respectively. bFGF and GFAP immunoreactivity within Cg2 and the medial preoptic area (MPOA) were measured. In both experiments astrocytic bFGF and GFAP surface density in the Cg2 varied significantly across groups. All postpartum rats, regardless of stage of lactation or presence of the litter, had significantly higher levels of bFGF and GFAP immunoreactivity than cycling animals. Thus, the maintenance of this upregulation in bFGF and GFAP immunoreactivity does not depend on suckling stimulation. Consistent with our previous report, astrocytic bFGF was also elevated in the MPOA of PP16 animals. These data suggest a robust, long-lasting, postpartum change in bFGF and GFAP immunoreactivity in Cg2 and a role for this area of the cortex in the physiological and behavioral adaptations that accompany reproductive experience.     

Chemosensory and hormone information are relayed directly between the medial amygdala, posterior bed nucleus of the stria terminalis, and medial preoptic area in male Syrian hamsters

In many rodent species, including Syrian hamsters, the expression of appropriate social behavior depends critically on the perception and identification of conspecific odors. The behavioral response to these odors is mediated by a network of steroid-sensitive ventral forebrain nuclei including the medial amygdala (Me), posterior bed nucleus of the stria terminalis (BNST), and medial preoptic area (MPOA). Although it is well-known that Me, BNST, and MPOA are densely interconnected and each uniquely modulates odor-guided social behaviors, the degree to which conspecific odor information and steroid hormone cues are directly relayed between these nuclei is unknown. To answer this question, we injected the retrograde tracer, cholera toxin B (CTB), into the BNST or MPOA of male subjects and identified whether retrogradely-labeled cells in Me and BNST 1) expressed immediate early genes (IEGs) following exposure to male and/or female odors or 2) expressed androgen receptor (AR). Although few retrogradely-labeled cells co-localized with IEGs, a higher percentage of BNST- and MPOA-projecting cells in the posterior Me (MeP) expressed IEGs in response to female odors than to male odors. The percentage of retrogradely-labeled cells that expressed IEGs did not, however, differ between and female and male odor-exposed groups in the anterior Me (MeA), posterointermediate BNST (BNSTpi), or posteromedial BNST (BNSTpm). Many retrogradely-labeled cells co-localized with AR, and a higher percentage of retrogradely-labeled MeP and BNSTpm cells expressed AR than retrogradely-labeled MeA and BNSTpi cells, respectively. Together, these data demonstrate that Me, BNST, and MPOA interact as a functional circuit to process sex-specific odor cues and hormone information in male Syrian hamsters.     

Amniotic fluid is important for the maintenance of maternal responsiveness and the establishment of maternal selectivity in sheep

Amniotic fluid (AF) is important for the establishment of maternal behaviour in inexperienced ewes, but its role in experienced mothers remains to be studied. Here, the maintenance of post-partum maternal responsiveness and the establishment of exclusive bonding was investigated in multiparous ewes when AF was removed from the neonate or/and physical contact with the young was precluded for the first 4 h post partum. Maintenance of maternal responsiveness and establishment of exclusive bonding were measured by the proportion of mothers accepting their own lamb and alien lambs that had been either washed or not washed, and by comparing an acceptance score for each type of lamb. The acceptance score was computed by summing standardised variables of acceptance (low bleats, acceptance at udder, nursing and licking time) and subtracting standardised variables of rejection (high-pitched bleats, rejection at the udder and aggressive behaviour). Washing the neonate reduced its acceptance score, but the proportion of mothers rejecting their own lamb was reduced only when washing the neonate and prevention of physical contact for 4 h were combined (7/15 v. 0/10 in controls, P = 0.02). In addition, washing the neonate increased the acceptance score of the washed alien lamb, but not of the unwashed alien. However, washing and privation of physical contact did not increase significantly the proportion of mothers accepting an alien lamb at 4 h post partum. We conclude that AF is important in experienced ewes for the establishment of maternal responsiveness, as already found in primiparous mothers. In addition, our results indicate that AF also carries some chemosensory information facilitating exclusive bonding.     

Parity-associated reductions in behavioral sensitivity to opiates

Behavioral and physiological responses differ between primiparous and multiparous female rodents. Specifically, multiparous females respond with the full repertoire of maternal behaviors much more rapidly and with greater intensity than their primiparous counterparts. Since opiates inhibit the expression of maternal behavior in postpartum rats and can be reversed by means of the opiate antagonist naloxone, we investigated whether multiparous females would be resistant to the inhibitory effects of opiates on maternal behavior, relative to primiparous females. In Experiment 1 we evaluated the effects of a range of doses of morphine sulfate (MS; 0.625, 1.25, 2.5, 5.0, and 10.0 mg/kg or saline) on maternal behavior in primiparous females on Days 5-6 of lactation. The 5.0 and 10.0 mg/kg doses effectively disrupted maternal behavior, whereas the lower doses were ineffective or only marginally disruptive. In Experiment 2, age-matched female rats were timed-mated and tested for maternal behavior from Day 5 to 13 of lactation, after daily injections of the 5.0 mg/kg dose of MS. On Day 5 of lactation, this morphine treatment eliminated full maternal behavior in 87% of the primiparous animals, but only 37% of the multiparous animals were affected. By Day 10 of lactation, 100% of the multiparous females displayed full maternal behavior after MS treatment, whereas only 69% of primiparous females were responsive. In Experiment 3, analgesic responses were measured both in rats experiencing their initial or second pregnancy, and in postpartum, lactating rats after MS (5.0 mg/kg) administration. Using a tail-flick apparatus to measure analgesia, we found multigravid females to be significantly less analgesic prepartum than primigravid females, suggesting less sensitivity to endogenous opioids.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of adrenalectomy and corticosterone replacement on maternal memory in postpartum rats

Hormones associated with parturition prime rats to behave maternally, although hormonal changes are not necessary for these behaviors to occur. Experience with pups after birth enhances maternal responsiveness after a period of isolation, creating a maternal memory. The purpose of this study was to determine the role of corticosterone in the formation of maternal memory. Adrenalectomy or sham surgeries were performed in late gestation with corticosterone or vehicle pellets being given to adrenalectomized rats. Pups were removed immediately following parturition, and half of the rats received 4 h of pup experience, while the other half received only brief pup experience associated with parturition. Ten days following pup experience, foster pups were given to all rats. Latency to become maternal and maternal behaviors on the first 2 days of re-exposure and the first two maternal days were recorded. Among adrenalectomized rats given corticosterone, 4-h experience with pups decreased maternal latency when compared to brief experience with pups. This maternal experience effect was not found in comparisons between adrenalectomized rats not given corticosterone. In addition, corticosterone decreased latencies regardless of pup experience. Corticosterone also increased maternal behavior upon initial exposure to foster pups. In conclusion, corticosterone enhanced maternal memory and initial maternal behavior in postpartum rats.     

Effects of sex, litter size and periconceptional ewe nutrition on the ewe–lamb bond

Undernutrition restricted to the time around conception in sheep alters endocrine and metabolic responses in the offspring. Studies in rats suggest that such an early insult can also alter the behaviour of the offspring. We studied the effects of mild maternal periconceptional undernutrition (10–15% body weight reduction) on the lamb's response to separation from and reunion with the mother, and on the ewe–lamb bond, evaluated as the preference for each other over an alien ewe/lamb in a test enclosure, at 24 h, 1 and 4 weeks of age. Lamb birth weight was not affected by maternal nutrition. Maternal periconceptional undernutrition did not affect the lambs’ responses to separation and reunion (number of vocalisations, times to leave pen and achieve proximity with ewes) or the bond between ewes and lambs (percentage of time spent near their own dam/lamb). However, there were effects of sex, litter size and time on lambs’ responses to separation and reunion and on the ewe–lamb bond. Female lambs vocalised more during separation (P ≤ 0.01) and left the holding pen faster than males (P ≤ 0.05), and twins vocalised more than singletons (P ≤ 0.05). The time to leave the holding pen, achieve proximity with the ewes and number of vocalisations decreased with increasing postnatal age of the lamb (all P ≤ 0.001). Ewes showed a stronger preference for the lamb at 24 h and 1 week than at 4 weeks postpartum (P ≤ 0.001), whereas lambs followed an opposite trend, showing a lower preference for the mother at 24 h and 1 week and increased preference at 4 weeks of age (P ≤ 0.001). We conclude that periconceptional undernutrition does not affect offspring response to separation from the mother or the bond between ewes and lambs, but that these behaviours are affected by sex and litter size for up to 4 weeks after birth.     

Antagonism of V1b receptors promotes maternal motivation to retrieve pups in the MPOA and impairs pup-directed behavior during maternal defense in the mpBNST of lactating rats

Recent studies using V1b receptor (V1bR) knockout mice or central pharmacological manipulations in lactating rats highlighted the influence of this receptor for maternal behavior. However, its role in specific brain sites known to be important for maternal behavior has not been investigated to date. In the present study, we reveal that V1bR mRNA (qPCR) and protein levels (Western blot) within either the medial preoptic area (MPOA) or the medial-posterior part of the bed nucleus of the stria terminalis (mpBNST) did not differ between virgin and lactating rats. Furthermore, we characterized the effects of V1bR blockade via bilateral injections of the receptor subtype-specific antagonist SSR149415 within the MPOA or the mpBNST on maternal behavior (maternal care under non-stress and stress conditions, maternal motivation to retrieve pups in a novel environment, maternal aggression) and anxiety-related behavior in lactating rats. Blocking V1bR within the MPOA increased pup retrieval, whereas within the mpBNST it decreased pup-directed behavior, specifically licking/grooming the pups, during the maternal defense test. In addition, immediately after termination of the maternal defense test, V1bR antagonism in both brain regions reduced nursing, particularly arched back nursing. Anxiety-related behavior was not affected by V1bR antagonism in either brain region. In conclusion our data indicate that V1bR antagonism significantly modulates different aspects of maternal behavior in a brain region-dependent manner.     

Postpartum changes in the GABAergic system in the bed nucleus of the accessory olfactory tract

The bed nucleus of the accessory olfactory tract (BAOT) is a sexually dimorphic structure which controls the inhibition/disinhibition of the medial preoptic area in the expression of maternal behavior. Therefore, in the present study we investigated sex differences and the modulation of gamma-aminobutiric-acid (GABA) in the BAOT during the first two postpartum days. Four groups of Wistar rats: control males, control females, 0 h postpartum females and 48 h postpartum females, were used in this experiment. Sex differences in glutamate decarboxylase (GAD) and GABA(A) alpha-chain receptor densities were apparent in the BAOT. The hormonal and behavioral postpartum state affects GABAergic activity in the females' BAOT in two ways: firstly, pregnancy and the first two postpartum days induce an increase in GABA(A)-receptor and GAD densities; secondly, the intensity of these activities are greater in the left hemisphere than in the right. These changes might be related to the BAOT's function of inhibiting/disinhibiting maternal behavior.     

Oxytocin receptors in the nucleus accumbens shell are involved in the consolidation of maternal memory in postpartum rats

Female rats with maternal experience display a shorter onset of maternal responsiveness compared to those with no prior experience. This phenomenon called ‘maternal memory’ is critically dependent on the nucleus accumbens (NA) shell. We hypothesized that activation of OT receptors in the NA shell facilitates maternal memory. In Experiment 1, postpartum female rats given 1 hour of maternal experience were infused following the experience with either a high or low dose of an OT antagonist into the NA shell and tested for maternal behavior after a 10-day pup isolation period. Females receiving a high dose of the antagonist showed a significantly longer latency to exhibit full maternal behavior after the pup isolation period compared to females that received vehicle or a high dose of antagonist in a control region. In Experiment 2, postpartum female rats were infused with either a high or low dose of OT into the NA shell after a 15-minute maternal experience and tested for maternal behavior after a 10-day pup isolation period. There were no significant differences between the females infused with OT and females treated with a vehicle infused into the NA shell or with OT infused into the control region. One possible reason for a lack of facilitation is a floor effect, since females in the control groups displayed a rapid maternal response after the pup isolation period. These findings suggest that OT receptors, likely in combination with other neurotransmitters, in the NA shell play a role in the consolidation of maternal memory.     

Pregnancy and maternal behavior induce changes in glia, glutamate and its metabolism within the cingulate cortex

An upregulation of the astrocytic proteins GFAP and bFGF within area 2 of the cingulate cortex (Cg2) occurs within 3 hours of parturition in rats. These changes are the result of an interaction between hormonal state and maternal experience and are associated with increased dendritic spine density in this area. Here, we examined whether this upregulation of astrocytic proteins generalized to other glial markers and, in particular those associated with glutamate metabolism. We chose glial markers commonly used to reflect different aspects of glial function: vimentin, like GFAP, is a marker of intermediate filaments; glutamine synthetase (GS), and S-100beta, are used as markers for mature astrocytes and GS has also been used as a specific marker for glutamatergic enzymatic activity. In addition, we examined levels of proteins associated with glutamine synthetase, glutamate, glutamine and two excitatory amino acid transporters found in astrocytes, glt-1 and glast. S100beta immunoreactivity did not vary with reproductive state in either Cg2 or MPOA suggesting no change in the number of mature astrocytes across these conditions. Vimentin-ir did not differ across groups in Cg2, but expression of this protein decreased from Day 1 postpartum onwards in the MPOA. By contrast, GS-ir was increased within 24 h postpartum in Cg2 but not MPOA and similarly to GFAP and bFGF this upregulation of GS resulted from an interaction between hormonal state and maternal experience. Within Cg2, upregulation of GS was not accompanied by changes in the astrocytic glutamatergic transporters, glt-1 and glast, however, an increase in both glutamate and glutamine proteins were observed within the Cg2 of postpartum animals. Together, these changes suggest postpartum upregulation of glutamatergic activity and metabolism within Cg2 that is stimulated by pregnancy hormones and maternal experience.