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Maternal interactions with offspring are highly rewarding, which reinforces expression of essential caregiving behaviours that promote offspring survival. In rats, the rewarding effect of pups depends on reproductive state, with lactating females specifically developing strong preferences for pup-associated contexts. Whether this also occurs in mice is unknown, hence we aimed to characterise pup-related preference across reproductive states in female mice. In a conditioned place preference (CPP) test, pups were a rewarding stimulus to female mice prior to lactation, with virgin and pregnant females developing a preference for a pup-associated context. We have previously shown that lactogenic hormones, acting through the prolactin receptor (Prlr), play an important role in maternal motivation. Here, we aimed to investigate whether Prlr action is important for pup-related reward behaviour in mice. We showed that prolactin itself had a reinforcing effect in a CPP test, and that exposure to pups increased blood prolactin levels in virgin female mice. Prlr expression in CamKIIα-expressing neurons and GABAergic neurons has previously been shown to be important for different aspects of parental behaviour. However, we found that conditional Prlr deletion from either of these neuronal populations did not disrupt the development of a preference for pup-associated contexts in pregnant female mice, indicating that lactogenic action on these populations is not necessary for the rewarding effect of pups. Together, these data show that while lactogenic hormones likely contribute to a rewarding effect of pups, their action on two key neuronal populations is not necessary for this effect in female mice., (© 2022 The Authors. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.)

Transition into motherhood involves profound physiological and behavioral adaptations that ensure the healthy development of offspring while maintaining maternal health. Dynamic fluctuations in key hormones during pregnancy and lactation induce these maternal adaptations by acting on neural circuits in the brain. Amongst these hormonal changes, lactogenic hormones (e.g., prolactin and its pregnancy-specific homolog, placental lactogen) are important regulators of these processes, and their receptors are located in key brain regions controlling emotional behaviors and maternal responses. With pregnancy and lactation also being associated with a marked elevation in the risk of developing mood disorders, it is important to understand how hormones are normally regulating mood and behavior during this time. It seems likely that pathological changes in mood could result from aberrant expression of these hormone-induced behavioral responses. Maternal mental health problems during pregnancy and the postpartum period represent a major barrier in developing healthy mother-infant interactions which are crucial for the child's development. In this review, we will examine the role lactogenic hormones play in driving a range of specific maternal behaviors, including motivation, protectiveness, and mother-pup interactions. Understanding how these hormones collectively act in a mother's brain to promote nurturing behaviors toward offspring will ultimately assist in treatment development and contribute to safeguarding a successful pregnancy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Georgescu, Swart, Grattan and Brown.)

The survival of newborn offspring in mammals is dependent on sustained maternal care. Mammalian mothers are highly motivated to interact with and care for offspring, however, it is unclear how hormonal signals act on neural circuitry to promote maternal motivation during the transition to motherhood. In this study we aimed to establish methods that enable us to evaluate change in maternal motivation across the reproductive life cycle in female mice. Using two behavioural testing paradigms; a novel T-maze retrieval test and a barrier climbing test, we found that pup retrieval behaviour was low in virgin and pregnant mice compared to lactating females, indicating that maternal motivation arises around the time of parturition. Furthermore, in reproductively experienced females, maternal motivation declined over time after weaning of pups. As we have previously shown that lactogenic action mediated through the prolactin receptor (Prlr) in the medial preoptic area (MPOA) is essential for the expression of maternal behaviour, we aimed to investigate the role of lactogenic hormones in promoting pup-related motivational behaviours. With GABAergic neurons expressing Prlr in multiple brain regions important for maternal behaviour, we conditionally deleted Prlr from GABA neurons. Compared to control females, lactating GABA neuron-specific Prlr knockout mice showed slower and incomplete pup retrieval behaviour in the T-maze test. Testing of anxiety behaviour on an elevated plus maze indicated that these mice did not have increased anxiety levels, suggesting that lactogenic action on GABA neurons is necessary for the full expression of motivational aspects of maternal behaviour during lactation., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Recently, the putative association between selective serotonin reuptake inhibitor (SSRI) exposure during pregnancy and the development of social disorders in children has gained increased attention. However, clinical studies struggle with the confounding effects of maternal depression typically co-occurring with antidepressant treatment. Furthermore, preclinical studies using an animal model of maternal depression to study effects of perinatal SSRI exposure on offspring social behavior are limited. Therefore, the aim of this study was to investigate effects of perinatal fluoxetine exposure on juvenile and adult social behavior in male and female rat offspring, using an animal model of maternal vulnerability. We exposed heterozygous serotonin transporter (SERT) deficient female rats to early life maternal separation stress, and used this as a model for maternal vulnerability. Control and early life stressed heterozygous serotonin transporter knockout (SERT) dams were treated with the SSRI fluoxetine or vehicle throughout gestation and lactation. Subsequently, both male and female wildtype (SERT +/+ ) and heterozygous (SERT +/- ) rat offspring were tested for pup ultrasonic vocalizations (USVs), juvenile social play behavior and adult social interaction. Fluoxetine treatment of the dams resulted in a reduced total USV duration in pups at postnatal day 6, especially in SERT +/+ males. Perinatal fluoxetine exposure lowered social play behavior in male offspring from both control and early life stressed dams. However, in females a fluoxetine-induced reduction in juvenile play behavior was only present in offspring from control dams. Offspring genotype did not affect juvenile play behavior. Despite fluoxetine-induced behavioral effects at juvenile age, fluoxetine reduced male adult social behavior in offspring from control dams only. Effects of fluoxetine on female adult social behavior were virtually absent. Interestingly, early life stress in dams increased adult social exploration in vehicle exposed SERT +/+ female offspring and total social behavior in fluoxetine exposed adult SERT +/- male offspring. Furthermore, SERT +/- males appeared less social during adulthood compared to SERT +/+ males. Overall, the present study shows that chronic blockade of the serotonin transporter by fluoxetine during early development has a considerable impact on pup USVs, juvenile social play behavior in both male and female offspring, and to a lesser extent on male social interaction in adulthood.

South African savanna grasslands are often characterised by indigestible tufted grass species whereas lawn grasses are far more desirable in terms of herbivore sustenance. We aimed to investigate the role of nutrients and/or the disturbance (grazing, trampling) by herbivores on the formation of grazing lawns. We conducted a series of common garden experiments to test the effect of nutrients on interspecific competition between a typical lawn-forming grass species (Cynodon dactylon) and a species that is frequently found outside grazing lawns (Hyparrhenia hirta), and tested for the effect of herbivore disturbance in the form of trampling and clipping. We also performed a vegetation and herbivore survey to apply experimentally derived insights to field observations. Our results showed that interspecific competition was not affected by soil nutrient concentrations. C. dactylon did show much more resilience to disturbance than H. hirta, presumably due to the regenerative capacity of its rhizomes. Results from the field survey were in line with these findings, describing a correlation between herbivore pressure and C. dactylon abundance. We conclude that herbivore disturbance, and not soil nutrients, provide C. dactylon with a competitive advantage over H. hirta, due to vegetative regeneration from its rhizomes. This provides evidence for the importance of concentrated, high herbivore densities for the creation and maintenance of grazing lawns.

We exhibit infinite families of two-dimensional lattices (some of which are triangulations or quadrangulations of the plane) on which the q-state Potts antiferromagnet has a finite-temperature phase transition at arbitrarily large values of q. This unexpected result is proven rigorously by using a Peierls argument to measure the entropic advantage of sublattice long-range order. Additional numerical data are obtained using transfer matrices, Monte Carlo simulation, and a high-precision graph-theoretic method.

CH31 B lymphomas represent a model for antigen-induced deletional tolerance of immature B lymphocytes, because cross-linking the B cell antigen receptor (BCR) induces G(1) phase arrest and apoptosis. We have recently demonstrated that BCR cross-linking leads to a transient activation of p38 mitogen-activated protein kinase (MAPK) in CH31 B cells. In this paper, we functionally characterize the role of p38 MAPK in BCR-induced apoptosis as well as evaluate the regulation of additional MAPKs by the BCR. We demonstrate that JNK and ERK activities are not affected by BCR cross-linking, suggesting that these MAPKs are not directly involved in initiating the apoptotic cascade. By contrast, we show that pretreatment of CH31 B cells with the highly specific p38 MAPK inhibitor SB203580 ablated both BCR-induced p38 MAPK activity and apoptosis. Pretreatment of CH31 cells with an inactive SB203580 analog, SB202474, did not prevent apoptosis. These findings establish a key role for p38 MAPK in antigen receptor-mediated apoptosis of CH31 B cells., (Copyright 2000 Academic Press.)

The cAMP response element (CRE) binding protein (CREB) is emerging as a key regulatory factor of gene transcription in B lymphocytes; however, the postreceptor pathways that regulate CREB activity and CRE-dependent gene transcription remain largely undefined. We investigated B cell Ag receptor (BCR)-mediated phosphorylation and activation of CREB in the surface IgM+ CH31 B cell lymphoma, which undergoes Ag-dependent cell death. The activity of p38 mitogen-activated protein kinase (MAPK) was increased in response to BCR ligation. Phosphorylation of CREB on serine 133, a modification that positively regulates its trans-activation, was concomitantly increased. Inhibition of p38 MAPK by pretreating CH31 B cells with the highly specific bicyclic imidazole inhibitor, SB203580, reduced BCR-induced CREB phosphorylation. BCR cross-linking also led to increased MAPK-activated protein kinase-2 activity, an enzyme that lies immediately downstream from p38 MAPK; MAPK-activated protein kinase-2 immune complexes phosphorylated a peptide substrate containing the CREB serine 133 phosphoacceptor motif. Given the role of CREB in regulating junB gene expression in mature B lymphocytes, we examined whether p38 MAPK activity was necessary for CRE-dependent junB transcription in CH31 B cells. BCR ligation led to increased junB mRNA levels, which were significantly reduced in CH31 B cells pretreated with SB203580. Activation of a CRE-dependent junB promoter/chloramphenicol acetyltransferase (CAT) reporter gene by the BCR was also blocked by SB203580. Similarly, inhibition of p38 MAPK in surface IgM+ WEHI-231 B cell lymphomas resulted in reduced BCR-induced junB mRNA expression and junB promoter activation. The results implicate a p38 MAPK pathway in BCR-mediated CREB phosphorylation and junB transcriptional activation in B cell lymphomas.

We demonstrate here that paclitaxel exposure to RPMI-1788 B lymphoblasts caused a dose- and time-dependent increase in nuclear factor activator protein 1 (AP-1) DNA binding activity. The basal DNA binding activities of nuclear factors NF-kappaB and Ets were not affected by paclitaxel. Consistent with these biochemical events, paclitaxel stimulated AP-1-dependent chloramphenicol acetyltransferase (CAT) reporter gene transcription in vivo, as directed from a tetradecanoyl phorbol acetate-inducible promoter. AP-1 binding activity of nuclear extracts isolated from paclitaxel treated cells was reduced following immunodepletion with antibodies directed against individual Jun family proteins, whereas anti-cFos, anti-Fra1, and anti-FosB antibodies were not inhibitory. Paclitaxel caused a rapid and transient increase in c-Jun NH2-terminal kinase (JNK) activity, a proposed mediator of stress activation pathways. By contrast, exposure to paclitaxel produced a transient reduction in the extracellular signal-regulated mitogen-activated protein kinase 2 (ERK2) activity, a proposed mediator of growth factor-stimulated proliferation pathways. Transient activation of the c-Jun-NH2-terminal kinase/AP-1 pathway, together with down-regulation of ERK2 activity, may be a key event in the early response of RPMI-1788 B lymphoblasts to paclitaxel exposure.