The maturational characteristics of the GABA input in the anterior piriform cortex may also contribute to the rapid learning of the maternal odor during the sensitive period.

During the first ten postnatal days (P), infant rodents can learn olfactory preferences for novel odors if they are paired with thermo-tactile stimuli that mimic components of maternal care. After P10, the thermo-tactile pairing becomes ineffective for conditioning. The current explanation for this change in associative learning is the alteration in the norepinephrine (NE) inputs from the locus coeruleus (LC) to the olfactory bulb (OB) and the anterior piriform cortex (aPC). By combining patch-clamp electrophysiology and computational simulations, we showed in a recent work that a transitory high responsiveness of the OB-aPC circuit to the maternal odor is an alternative mechanism that could also explain early olfactory preference learning and its cessation after P10. That result relied solely on the maturational properties of the aPC pyramidal cells. However, the GABAergic system undergoes important changes during the same period. To address the importance of the maturation of the GABAergic system for early olfactory learning, we incorporated data from the GABA inputs, obtained from in vitro patch-clamp experiment in the aPC of rat pups aged P5-P7 reported here, to the model proposed in our previous publication. In the younger than P10 OB-aPC circuit with GABA synaptic input, the number of responsive aPC pyramidal cells to the conditioned maternal odor was amplified in 30% compared to the circuit without GABAergic input. When compared with the circuit with other younger than P10 OB-aPC circuit with adult GABAergic input profile, this amplification was 88%. Together, our results suggest that during the olfactory preference learning in younger than P10, the GABAergic synaptic input presumably acts by depolarizing the aPC pyramidal neurons in such a way that it leads to the amplification of the pyramidal neurons response to the conditioned maternal odor. Furthermore, our results suggest that during this developmental period, the aPC pyramidal cells themselves seem to resolve the apparent lack of GABAergic synaptic inhibition by a strong firing adaptation in response to increased depolarizing inputs.

Postnatal development of inhibitory synaptic transmission in the anterior piriform cortex.

The morphological and functional development of inhibitory circuit in the anterior piriform cortex (aPC) during the first three postnatal weeks may be crucial for the development of odor preference learning in infant rodents. As first step toward testing this hypothesis, we examined the normal development of GABAergic synaptic transmission in the aPC of rat pups during the postnatal days (P) 5-8 and 14-17. Whole cell patch-clamp recordings of layer 2/3 (L2/3) aPC pyramidal cells revealed a significant increase in spontaneous (sIPSC) and miniature (mIPSC) inhibitory postsynaptic current frequencies and a decrease in mIPSC rise and decay-time constant at P14-P17. Moreover, as the development of neocortical inhibitory circuit can be driven by sensory experience, we recorded sIPSC and mIPSC onto L2/3 aPC pyramidal cells from unilateral naris-occluded animals. Early partial olfactory deprivation caused by naris occlusion do not affected the course of age-dependent increase IPSC frequency onto L2/3 aPC pyramidal cell. However, this age-dependent increase of sIPSC and mIPSC frequencies were lower on aPC pyramidal cells ipsilateral to the occlusion side. In addition, the age-dependent increase in sIPSC frequency and amplitude were more pronounced on aPC pyramidal cells contralateral to the occlusion. While mIPSC kinetics were not affected by age or olfactory deprivation, at P5-P8, the sIPSC decay-time constant on aPC pyramidal cells of both hemispheres of naris-occluded animals were significantly higher when compared to sham. These results demonstrated that the GABAergic synaptic transmission on the aPC changed during postnatal development by increasing inhibitory inputs on L2/3 pyramidal cells, with increment in frequency of both sIPSC and mIPSC and faster kinetics of mIPSC. Our data suggested that the maturation of GABAergic synaptic transmission was little affected by early partial olfactory deprivation. These results could contribute to unravel the mechanisms underlying the development of odor processing and olfactory preference learning.

The Impact of Oxytocin Gene Knockout on Sexual Behavior and Gene Expression Related to Neuroendocrine Systems in the Brain of Female Mice.

Social relations are built and maintained from the interaction among individuals. The oxytocin (OT), vasopressin (VP), estrogen, dopamine, and their receptors are involved in the modulation of sexual behavior in females. This study aimed to analyze the impact of OT gene knockout (OTKO) on sexual behavior and the gene expression of oxytocin (OTR), estrogen alpha (ERα), estrogen beta (ERß), vasopressin (V1aR), and dopamine (D2R) receptors in the olfactory bulb (OB), prefrontal cortex (PFC), hippocampus (HPC), and hypothalamus (HPT), as well as in the synthesis of VP in the HPT of female mice. Wild-type (WT) littermates were used for comparisons. The CDNAs were synthesized by polymerase chain reaction and the gene expression was calculated with the 2-ΔΔCt formula. Our results showed that the absence of OT caused an increase in the frequency and duration of non-receptive postures and a decrease in receptive postures in the OTKO. OTKO females showed a significant decrease in the gene expression of OTR in the HPC, V1aR in the HPT, and ERα and ERß in the PFC. There was no significant difference in the gene expression of D2R of OTKO. However, OTKO showed an increased gene expression of V1aR in the HPC. There is no significant difference in VP mRNA synthesis in the HPT between OTKO and WT. Our findings demonstrate that the absence of OT leads to significant changes in the expression of the studied genes (OTR, ERα, ERß, V1aR), and these changes may contribute to the decreased sexual behavior observed in OTKO females.

Intervention with the mother-infant relationship reduces cell proliferation in the Locus Coeruleus of female rat pups.

The Locus Coeruleus (LC) is a noradrenergic nucleus involved in several neuroendocrine and behavioral functions. During the neonatal period, the LC is critical for olfactory learning. Full development occurs during the early postnatal period. Environmental interventions after birth may affect neurogenesis. In rats, the neonatal handling procedure has been used as a model to analyze the effects of environmental intervention early in life. It has been related to several long-lasting behavioral and neuroendocrine changes. The present study analyzed the effects of handling on the number of neurons, cellular proliferation, and apoptosis in the LC of 11-day-old female rats. Wistar rat pups were submitted to brief maternal separation followed by handling (1 min per day from postnatal day [PND] 1 to 10). On PND 11, the LC was analyzed using immunohistochemistry for NeuN and BrdU, TUNEL staining, and electron microscopy. The intervention reduced the number of neurons in the LC but showed no significant change in the number of apoptotic cells, as measured by the TUNEL technique. However, the number of proliferating cells was significantly lower in the handled rat pups as compared with the nonhandled ones. This study demonstrates that the infant LC is sensitive to changes in maternal behavior. A seemingly mild environmental intervention during the neonatal period may reprogram the development of the LC, altering cell proliferation. (PsycINFO Database Record

Effects of sleep restriction during pregnancy on the mother and fetuses in rats.

The present study aimed to analyze the effects of sleep restriction (SR) during pregnancy in rats. The following three groups were studied: home cage (HC pregnant females remained in their home cage), Sham (females were placed in tanks similar to the SR group but with sawdust) and SR (females were submitted to the multiple platform method for 20 h per day from gestational days (GD) 14 to 20). Plasma corticosterone after 6 days of SR was not different among the groups. However, the relative adrenal weight was higher in the SR group compared with the HC group, which suggests possible stress impact. SR during pregnancy reduces the body weight of the female but no changes in liver glycogen, cholesterol and triglycerides, and muscle glycogen were detected. On GD 20, the fetuses of the females submitted to SR exhibited increased brain derived neurotrophic factor (BDNF) in the hippocampus, which indicates that sleep restriction of mothers during the final week of gestation may affect neuronal growth factors in a fetal brain structure, in which active neurogenesis occurs during the deprivation period. However, no changes in the total reactive oxygen species (ROS) in the cortex, hippocampus, or cerebellum of the fetuses were detected. SR females showed no major change in the maternal behavior, and the pups' preference for the mother's odor on postpartum day (PPD) 7 was not altered. On GD 20, the SR females exhibited increased plasma prolactin (PRL) and oxytocin (OT) compared with the HC and Sham groups. The negative outcomes of sleep restriction during delivery could be related, in part, to this hormonal imbalance. Sleep restriction during pregnancy induces different changes compared with the changes described in males and affects both the mother and offspring.

Gene expression in the CNS of lactating rats with different patterns of maternal behavior.

For most mammalian species, maternal behavior has an essential role in the development of the offspring. The frequency of licking/grooming (LG) the pups has been used as a parameter to evaluate maternal care, having mothers with high (HL) or low (LL) frequencies of LG. This study aimed to analyze the gene expression of the receptors for dopamine (Drd1a), prolactin (Prlr), serotonin (Htr1a, Htr1b), estrogen (Esr1, Esr2), and of Bdnf in the olfactory bulb (OB), hippocampus (HP), prefrontal cortex (PFC), and striatum (ST) of Wistar rats from three groups: LL (n = 8); HL (n = 8); virgin females in diestrus (D; n = 6). Maternal behavior was studied between the 1st and 7th postpartum days. Brain parts were analyzed by qRT-PCR. LL showed a decrease in the frequency of nursing, and an increase of remaining off the pups. There was an increase in gene expression of Drd1a, Prlr, Htr1a, Htr1b and Esr1 in the OB of HL, compared to LL. In the HP, Drd1a, Prlr and Htr1a were differently expressed when comparing HL, or LL, with D. The main finding is that HL had higher gene expression levels in the OB, which is a crucial structure to promote behavioral differences.

Serum NGF, BDNF and IL-6 levels in postpartum mothers as predictors of infant development: the influence of affective disorders.

BACKGROUND: Early adverse experiences are associated with increased risk of developing psychiatric disorders, although little is known about the neurobiological mediators involved. The mechanisms by which early environmental influences may mediate vulnerability in the development of offspring await further investigation. The present study correlated the NGF, BDNF, IL-6 and cortisol levels of mothers with postpartum affective disorders (PPAD) with infant development. METHODS: A longitudinal study was performed with 152 pregnant women and their infants. Between 60 and 120 days after delivery, women were interviewed and provided biological samples for biochemical analysis, and the infants were examined for neurobiological-motor development. RESULTS: Overall, the mothers' history of affective disorders, PPAD and anxiety disorder were associated with infant motor development. Using an adjusted linear regression analysis, PPAD (p = 0.049), maternal anxiety disorder (p = 0.043), NGF level (p = 0.034) and infant cortisol level (p = 0.013) were associated with infant motor development. Using a factorial analysis of primary components, two components were retained. The psychological factor was characterized by a positive loading of a history of affective disorder, PPAD and anxiety disorder. For the biological factor, infant cortisol adhered negatively with infant motor development, but NGF was positively associated. The psychological factor had a negative association, but the biological factor had a positive association with infant motor development. CONCLUSIONS: There are few studies that have focused on the relationship of biomarkers and infant neurodevelopment. Our study points that psychological and biological factors are associated with infant motor development, however the causal relationship between these factors is still to be defined.

Aggression-reducing effects of F15599, a novel selective 5-HT1A receptor agonist, after microinjection into the ventral orbital prefrontal cortex, but not in infralimbic cortex in male mice.

BACKGROUND: The 5-HT1A receptor subtype has been postulated to modulate aggressive behavior particularly when it is excessive. F15599 is a high affinity and selective 5-HT1A receptor agonist that exhibits biased agonism for postsynaptic receptors that are preferentially coupled to Gαi3 protein subunits, with more potent action in the cortex, and with potential for selectively reducing aggression. OBJECTIVES AND METHODS: The aims of the current study were to investigate the anti-aggressive effects of the novel 5-HT1A receptor agonist, F15599, microinjected into the ventral orbital prefrontal cortex (VO PFC) and into the infralimbic cortex (ILC) of CF-1 male mice that had been previously socially provoked and to confirm the specific action at this receptor by blocking its effects using the 5-HT1A receptor antagonist, WAY100,635. RESULTS: Microinjection of the lower doses of F15599 (0.03 and 0.1 µg) into the VO PFC, but not into the ILC, significantly reduced the frequency of attack bites and sideways threats, without affecting other elements of the behavioral repertoire related to aggression such as pursuing and sniffing the intruder and tail rattle. There were also no changes observed in the duration of walking and rearing. Pretreatment with WAY100,635 prevented the anti-aggressive effects of F15599 when microinjected into VO PFC. CONCLUSIONS: The present results demonstrated that F15599 is effective in reducing the most intense behavioral elements of aggressive behavior in male mice, when microinjected into the VO PFC, but not into the ILC, without affecting nonaggressive behavior, and confirmed the critical role of this cortical region and specifically the 5-HT1A heteroreceptors in the modulation of escalated aggressive behavior.

Fos expression in the prefrontal cortex and mesencephalic dorsal raphe nucleus in lactating rats after social instigation

Females are often less aggressive than males, but they exhibit high levels of agonistic behavior against an intruder in the area of ​​the nest during lactation. This behavior is referred to as maternal aggression. In rats, maternal aggressive behavior occurs more often from postpartum day 3 (PPD 3) to PPD 12. Social instigation is an experimental protocol used to increase the levels of aggression that are typical of the species. In the present study we used social instigation to analyze the expression of a marker of neuronal activity, c-fos. Lactating rats on PPD 5, in the presence of their pups, were divided into four groups: (1) no social instigation and no aggressive behavior, (2) social instigation and no aggressive behavior, (3) no social instigation and aggressive behavior, and (4) social instigation and aggressive behavior. Sixty minutes after the aggression test we used immunohistochemistry to detect Fos in two brain regions, the ventral-orbital region of the prefrontal cortex (VO PFC) and dorsal raphe nucleus (DRN). Our results showed that rats with aggressive behavior that were provoked exhibited an increase in Fos expression in the VO PFC compared with the control group (i.e., no social instigation and no aggressive behavior). No change in Fos expression was found in the DRN. These results complement previous findings with microinjection of serotonin 5-hydroxytryptamine-1B receptor agonists into the same region, demonstrating that the VO PFC is an important region in the modulation of maternal aggressive behavior.

Fos expression in the prefrontal cortex and mesencephalic dorsal raphe nucleus in lactating rats after social instigation

Females are often less aggressive than males, but they exhibit high levels of agonistic behavior against an intruder in the area of ​​the nest during lactation. This behavior is referred to as maternal aggression. In rats, maternal aggressive behavior occurs more often from postpartum day 3 (PPD 3) to PPD 12. Social instigation is an experimental protocol used to increase the levels of aggression that are typical of the species. In the present study we used social instigation to analyze the expression of a marker of neuronal activity, c-fos. Lactating rats on PPD 5, in the presence of their pups, were divided into four groups: (1) no social instigation and no aggressive behavior, (2) social instigation and no aggressive behavior, (3) no social instigation and aggressive behavior, and (4) social instigation and aggressive behavior. Sixty minutes after the aggression test we used immunohistochemistry to detect Fos in two brain regions, the ventral-orbital region of the prefrontal cortex (VO PFC) and dorsal raphe nucleus (DRN). Our results showed that rats with aggressive behavior that were provoked exhibited an increase in Fos expression in the VO PFC compared with the control group (i.e., no social instigation and no aggressive behavior). No change in Fos expression was found in the DRN. These results complement previous findings with microinjection of serotonin 5-hydroxytryptamine-1B receptor agonists into the same region, demonstrating that the VO PFC is an important region in the modulation of maternal aggressive behavior.(AU)

Prenatal stress produces social behavior deficits and alters the number of oxytocin and vasopressin neurons in adult rats.

The present study investigated the long-lasting effects of prenatal repeated restraint stress on social behavior and anxiety, as well as its repercussions on oxytocin (OT) and vasopressin (VP)-positive neurons of the paraventricular (PVN) and supraoptic (SON) nuclei from stressed pups in adulthood. Female Wistar rats were exposed to restraint stress in the last 7 days of pregnancy. At birth, pups were cross-fostered and assigned to the following groups: prenatally non-stressed offspring raised by prenatally non-stressed mothers (NS:NS), prenatally non-stressed offspring raised by prenatally stressed mothers (S:NS), prenatally stressed offspring raised by prenatally non-stressed mothers (NS:S), prenatally stressed offspring raised by prenatally stressed mothers (S:S). As adults, male prenatally stressed offspring raised both by stressed mothers (S:S group) and non-stressed ones (NS:S group) showed impaired social memory and interaction. In addition, when both adverse conditions coexisted (S:S group), increased anxiety-like behavior and aggressiveness was observed in association with a decrease in the number of OT-positive magnocellular neurons, VP-positive magnocellular and parvocellular neurons of the PVN. The NS:S group exhibited a reduction in the amount of VP-positive magnocellular neurons compared to the S:NS. Thus, the social behavior deficits observed in the S:S and NS:S groups may be only partially associated with these alterations to the peptidergic systems. No changes were shown in the OT and VP cellular composition of the SON nucleus. Nevertheless, it is clear that a special attention should be given to the gestational period, since stressful events during this time may be related to the emergence of behavioral impairments in adulthood.

Association of a serotonin transporter gene polymorphism (5-HTTLPR) and stressful life events with postpartum depressive symptoms: a population-based study.

We conducted a cross-sectional study nested within a cohort study with 276 postpartum women to evaluate the role of a serotonin transporter gene polymorphism (5-HTTLPR) and the stressful life events (SLE) on the risk of postpartum depression (PPD) symptoms in a community sample. Participants were assessed between 45 and 90 days after delivery with the Edinburgh Postnatal Depression Scale (EPDS) and the Mini International Neuropsychiatric Interview (MINI). Data regarding socio-demographic variables, alcohol consumption, tobacco smoking and SLE occurring during pregnancy, were also collected. In the adjusted analysis, the women carrying the long (L) allele (LL) who experienced SLE showed higher prevalence ratios (PR) for PPD symptoms (EPDS ≥13) than those with two copies of the short (S) allele (SL) (PR = 9.91; 95% confidence interval: 1.70-57.87). In contrast, a trend of association was found between prior history of major depressive disorder (MDD) and the S allele carrier status (p = 0.07). No association was found between the formal diagnosis of current MDD and the 5-HTTLPR genotypes. In line with previous reports, we find in this sample that the L allele carrier status was associated with a heighten risk of depressive symptoms in postpartum when SLE were experienced during pregnancy.

Oxytocin modulates social interaction but is not essential for sexual behavior in male mice.

Recently, several studies have shown different conclusions regarding the effect of oxytocin (OT) on the social behaviors of male mice. Most of these studies used exogenous OT, but currently, investigations of the neural bases of social behavior are increasingly employing gene inactivation. This study aimed to analyze the role of OT in the modulation of social behaviors (i.e., sexual and social interaction behaviors) in male mice with selective deletions of the OT gene (OTKO) and the influence of this deletion in basal vasopressin (AVP) plasma concentrations. Our results showed that in the social interaction test, OTKO mice exhibited lower levels of social behaviors and higher levels of non-social behaviors compared to the wild type (WT) group. Additionally, the OTKO group showed a decrease in the number of agonistic behaviors delivered, and consequently, their dominance score was lower than that of the WT group. In the ethological analysis, the OTKO group had a lower aggressive performance and increased social investigation than the WT group. No significant differences were observed in the sexual behavior between groups. Finally, we found lower AVP plasma concentrations in the OTKO compared with the WT group. In conclusion, our data suggest that OT modulates social investigation behavior and the aggressiveness of male mice. The decrease in AVP concentrations in the OTKO group allows us to infer that AVP is physiologically relevant to these behavioral modulations. However, sexual behaviors do not seem to be affected by the lack of OT or by a decrease in the AVP concentration.

Neonatal handling induces deficits in infant mother preference and adult partner preference.

Neonatal handling is an experimental procedure used to understand how early-life adversity can negatively affect neurobehavioral development and place animals on a pathway to pathology. Decreased preference for the maternal odor during infancy is one of many behavioral deficits induced by neonatal handling. Here, we hypothesize that deficits in maternal odor preference may interfere with partner preference in the adult. To test this hypothesis, we assessed infant maternal odor preference and adult partner preference in different reproductive stages in both male and female rats that received neonatal handling. Our results indicate that only neonatally handled females present deficits in maternal odor preference during infancy, but both male and females present deficits in adult partner preference. However, sexual experience was effective in rescuing partner preference deficits in males. These results indicate that, considering infant and adult social interactions, females are more susceptible to the effects of neonatal handling than males.

Brain-derived neurotrophic factor levels in women with postpartum affective disorder and suicidality.

Our aim was to investigate serum brain-derived neurotrophic factor (BDNF) levels in postpartum women, according to the presence of postpartum affective disorder (PPAD) and suicidality. A cross-sectional study was carried out with women between 45 and 90 days after delivery. PPAD (depression, manic and mixed episode) and suicide risk were assessed using the Mini International Neuropsychiatric Interview. BDNF was assessed using a commercial ELISA kit. Linear regression was used for multivariate analyses. A hundred ninety women participated in the study, 15.3 % had PPAD, 7.4 % showed PPAD with suicide risk. BDNF levels were lower in subjects with three or more Stressful Life Events (P = 0.01). The serum BDNF levels of women with PPAD presenting suicide risk were significantly lower than those of women without suicide risk (1.50 ± 1.38 and 2.33 ± 1.28 ng/ml, P = 0.02). Clinicians should enquire postpartum women about their history of stressful life events, PPAD, and suicidality. This study shows the potential role of BDNF in the neurobiology of the association of PPAD and suicidality.

The role of AT1 receptor-mediated reproductive function in renovascular hypertension in male rats.

There is an association between hypertension and reproductive dysfunction. Angiotensin II (Ang II) is involved in the pathogenesis of hypertension and the regulation of reproduction. The present study aimed to determine whether the angiotensinergic system mediates the effects of hypertension on reproductive function in male rats subjected to a two-kidney, one-clip (2K1C) model. Sexual behavior parameters, gametogenesis and plasma concentrations of Ang II, testosterone, prolactin and corticosterone were evaluated in male rats 28days after 2K1C or sham surgery and losartan (Los) treatment (a type 1 angiotensin II (AT1) receptor antagonist) or vehicle (V) treatment. The animals were divided into Sham+V, 2K1C+V, Sham+Los and 2K1C+Los groups. The 2K1C+V group showed a hypertensive response, inhibition of sexual behavior, spermatogenesis dysfunction, and increases in plasma Ang II and prolactin. Conversely, plasma testosterone decreased, and plasma corticosterone remained constant. Losartan treatment normalized blood pressure and prevented the changes in plasma testosterone and prolactin, sexual behavior and spermatogenesis in the 2K1C+Los group. In addition, losartan treatment caused an additional increase in circulating Ang ll in both groups (Sham+Los and 2K1C+Los). Together, these results suggest that Ang ll, acting through the AT1 receptor, modulates behavioral and endocrine parameters of reproductive function during renovascular hypertension. In addition, the effects of circulating Ang II on plasma testosterone and prolactin seem to contribute to the spermatogenic and sexual dysfunctions in hypertensive rats.

Prenatal stress produces sex differences in nest odor preference.

Prenatal stress (PS) and early postnatal environment may alter maternal care. Infant rats learn to identify their mother through the association between maternal care and familiar odors. Female Wistar rats were exposed to restraint stress for 30 min, 4 sessions per day, in the last 7 days of pregnancy. At birth, pups were cross-fostered and assigned to the following groups: prenatal non-stressed mothers raising non-stressed pups (NS:NS), prenatal stressed mothers raising non-stressed pups (S:NS), prenatal non-stressed mothers raising stressed pups (NS:S), prenatal stressed mothers raising stressed pups (S:S). Maternal behaviors were assessed during 6 postpartum days. On postnatal day (PND) 7, the behavior of male and female pups was analyzed in the odor preference test; and noradrenaline (NA) activity in olfactory bulb (OB) was measured. The results showed that restraint stress increased plasma levels of corticosterone on gestational day 15. After parturition, PS reduced maternal care, decreasing licking the pups and increasing frequency outside the nest. Female pups from the NS:S, S:NS, S:S groups and male pups from the S:S group showed no nest odor preference. Thus, at day 7, female pups that were submitted to perinatal interventions showed more impairment in the nest odor preference test than male pups. No changes were detected in the NA activity in the OB. In conclusion, repeated restraint stress during the last week of gestation reduces maternal care and reduces preference for a familiar odor in rat pups in a sex-specific manner.

Analysis of transcriptional levels of the oxytocin receptor in different areas of the central nervous system and behaviors in high and low licking rats.

The natural variation in maternal care is an interesting model to analyze the physiological mechanisms that lead to differences in the mother-infant interaction. Several studies have shown differences in the expression of brain receptors such as the dopamine, estrogen and oxytocin receptors in areas classically involved in the onset and/or maintenance of maternal behavior: the medial preoptic area, the nucleus accumbens, the amygdala, the lateral septum, and the bed nucleus of the stria terminalis. The present study examined the responses of HL and LL rats in several behavioral tests and analyzes the transcription of the oxytocin receptor (OXTR) in the olfactory bulb (OB), the prefrontal cortex (FPC), the hippocampus (HP) and the striatum (ST) in different patterns of licking behavior. Our results showed that, in the second week postpartum, HL and LL mothers did not show behavioral differences in the elevated plus maze (EPM), the forced swimming test (FST) or the open field test. In the maternal aggressive behavior test, HL females showed a higher frequency of biting compared to LL females, but no significant differences in other aggressive behaviors were detected. LL mothers had higher levels of transcriptional OXTR in the OB and in the HP when compared to HL mothers. No differences in other areas were detected when compared LL and HL. These findings suggest that variations in maternal behavior may be associated with biting behavior of mothers and that OXTR participates in modulation of maternal behavior in rats, while other emotional behaviors are less related to such behavior.

Association between Na⁺,K⁺-ATPase activity and the vulnerability/resilience to mood disorders induced by early life experience.

There is increasing evidence that early life events can influence neurodevelopment and later susceptibility to disease. Chronic variable stress (CVS) has been used as a model of depression. The objective of this study was to evaluate the interaction between early experience and vulnerability to chronic variable stress in adulthood, analyzing emotional, metabolic and neurochemical aspects related to depression. Pups were (1) handled (10 min/day) or (2) left undisturbed from day 1 to 10 after birth. When the animals reached adulthood, the groups were subdivided and the rats were submitted or not to CVS, which consisted of daily exposure to different stressors for 40 days, followed by a period of behavioral tasks, biochemical (plasma corticosterone and insulin sensitivity) and neurochemical (Na⁺,K⁺-ATPase activity in hippocampus, amygdala and parietal cortex) measurements. Neonatally-handled rats demonstrated shorter immobility times in the forced swimming test, independently of the stress condition. There was no difference concerning basal corticosterone or insulin sensitivity between the groups. Na⁺,K⁺-ATPase activity was decreased in hippocampus and increased in the amygdala of neonatally-handled rats. CVS decreased the enzyme activity in the three structures, mainly in the non-handled group. These findings suggest that early handling increases the ability to cope with chronic variable stress in adulthood, with animals showing less susceptibility to neurochemical features associated with depression, confirming the relevance of the precocious environment to vulnerability to psychiatric conditions in adulthood.

Effect of social instigation and aggressive behavior on hormone levels of lactating dams and adult male Wistar rats

Among rodents, maternal aggression in the postpartum period represents a species-typical adaptation, but when aggressive behavior increases beyond this adaptive level, it can represent a model of excessive aggression. This study assessed the neuroendocrine response of lactating rats and socially instigated male rats. The aim of the present study was to assess neuroendocrine responses and the behavioral pattern of lactating rats and males that were subjected to an emotional stressor using the social instigation protocol. We measured plasma corticosterone levels as the key hormonal parameter of the hypothalamic-pituitary-adrenal (HPA) axis and oxytocin, prolactin, and progesterone, which are released in response to several types of stressors. Our results showed that lactating rats that were subjected to only social instigation or aggressive confrontation in the presence of their pups had lower plasma corticosterone levels, and this response was similar to oxytocin, prolactin, and progesterone levels. By contrast, male rats showed increased corticosterone levels after being subjected only to social instigation. Male rats also engaged in aggressive behavior compared with the control group. In conclusion, this study demonstrated that lactating rats subjected to social instigation exhibited an attenuation of the HPA axis response, which is considered to be crucial to the dam's welfare so that it can care for its offspring. Thus, we can infer that lactation is a relevant factor in neuroendocrine responses to stress because of the increased levels of corticosterone in males.