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This paper focuses upon representations of the figure of the tramp in interwar social exploration literature. It begins by exploring disciplinary attempts to highlight the apparent failure of the homeless to contribute within early social exploration literature, offering James Greenwood as an example. It then investigates Mark Freeman's claims regarding a tendency in later pre-war texts within the genre towards greater levels of personal identification – before using the example of Mary Higgs to suggest that the disciplinary impulse nonetheless remained in such works. In then looking at interwar social exploration texts by Frank Jennings, Frank Gray and George Orwell, an argument is developed that during the interwar period the tendency noted by Freeman was significantly heightened, as authors went to much greater lengths to understand the experience of being homeless. Ultimately, however, this development is seen to have done little to alter the disciplinary outlook of these authors. On the contrary, it is argued that in broadcasting their allegiance to the poor their texts can be seen to indicate the emergence of a survival strategy that enabled the perpetuation of a productivist agenda in the face of working-class enfranchisement and political representation – a strategy that this essay terms disciplinary subterfuge. [ABSTRACT FROM AUTHOR]

Paul Hindemith is hardly remembered for his music prior to the 1940s. During the Nazi occupation of Germany in the early 20th century, Paul Hindemith, reviled for his modernistic styles and relation to his Jewish wife, was forced to emigrate out of the Third Reich for his safety. Hindemith was known for his connections to New Objectivity, Gebrachsmusik, and tonality instability placed him in the wrong realm of composition in the Nazi’s minds. As Hitler rose to power in 1933, Hindemith knew he would need a composition to prove his worth amongst the Nazis. As such, Hindemith attempted to change his tides through the composition of the opera/symphony Mathis der Maler. Mathis featured the strong tonality, German nationalism, and Romantic monumentality the Nazis were hoping for to strengthen their regime and the global understanding of German culture. However, Mathis also illustrated Hindemith’s personal pains and struggles with the Reich.

The journalist Robert Sherard was committed to reworking the familiar slum-exploration narrative into a self-consciously crafted, even lyric genre. Guided by his identification as a bohemian aesthete, he employed high-literary allusions to elicit readers' compassion for the poor. When he moved from the early industrial exposé of The White Slaves of England to projects less focused on specific trades and their locales, he was forced to cover wider geographic ground and work on a tighter schedule. Granted less time to get to know poor locals, he felt wary and vulnerable among them, forgoing incognito slumming after briefly attempting it. Sherard resorted to a more conservative judgment of the poor, devising a set of signs by which to read and interpret their morality from a distance. In particular, he revived the mid-Victorian concept of moral character as a tool for understanding and justifying their degradation. At the heart of Sherard's slum writing is the tension inherent in flâneurie in practice: the desire to achieve an incisive observation of the crowd and a resistance to being subsumed in it. Ultimately, his slum prose reflects his struggles as he sought to reconcile his identities as an investigative journalist, an urban flaneur, and an aesthetic prose stylist. [ABSTRACT FROM AUTHOR]

Highlights • Conditioned place preference of social interaction does not distinguish various facets of social motivation. • Conventional classical conditioning paradigm can isolate social exploration from other social motivations. • Social exploration not tainted by other motivations such as social play was classically conditioned to a phasic cue. • Extinction and spontaneous recovery of social exploration was observed. Abstract Social conditioned place preference (SCPP) studies show that the reward value of social interaction is amenable to the laws of associative learning, such that it becomes associated with the physical properties of the context. However, social interaction can be initiated and maintained by a variety of motivations, such as the exploration of a novel conspecific, aggression, mutual grooming and mating-like actions. In order to study whether social exploration is rewarding, we used a conventional Pavlovian conditioning procedure in which access to a restrained same-sex rat served as a reward. Three dependent variables in two experiments showed that the reward value of social exploration becomes conditioned to a transient cue, and it is also subject to extinction and spontaneous recovery. The results may help to elucidate the mixed results obtained with SCPP procedures. [ABSTRACT FROM AUTHOR]

Paul Hindemith is hardly remembered for his music prior to the 1940s. During the Nazi occupation of Germany in the early 20th century, Paul Hindemith, reviled for his modernistic styles and relation to his Jewish wife, was forced to emigrate out of the Third Reich for his safety. Hindemith was known for his connections to New Objectivity, Gebrachsmusik, and tonality instability placed him in the wrong realm of composition in the Nazi's minds. As Hitler rose to power in 1933, Hindemith knew he would need a composition to prove his worth amongst the Nazis. As such, Hindemith attempted to change his tides through the composition of the opera/symphonyMathis der Maler.Mathis featured the strong tonality, German nationalism, and Romantic monumentality the Nazis were hoping for to strengthen their regime and the global understanding of German culture. However,Mathis also illustrated Hindemith's personal pains and struggles with the Reich. [ABSTRACT FROM AUTHOR]

Ethanol and caffeine are frequently consumed in combination and have opposite effects on the adenosine system: ethanol metabolism leads to an increase in adenosine levels, while caffeine is a non-selective adenosine A1/A2A receptor antagonist. These receptors are highly expressed in striatum and olfactory tubercle, brain areas involved in exploration and social interaction in rodents. Ethanol modulates social interaction processes, but the role of adenosine in social behavior is still poorly understood. The present work was undertaken to study the impact of ethanol, caffeine and their combination on social behavior, and to explore the involvement of A1 and A2A receptors on those actions. Male CD1 mice were evaluated in a social interaction three-chamber paradigm, for preference of conspecific vs. object, and also for long-term recognition memory of familiar vs. novel conspecific. Ethanol showed a biphasic effect, with low doses (0.25 g/kg) increasing social contact and higher doses (1.0-1.5 g/kg) reducing social interaction. However, no dose changed social preference; mice always spent more time sniffing the conspecific than the object, independently of the ethanol dose. Ethanol, even at doses that did not change social exploration, produced amnestic effects on social recognition the following day. Caffeine reduced social contact (15.0-60.0 mg/kg), and even blocked social preference at higher doses (30.0-60.0 mg/kg). The A1 antagonist CPT (3-9 mg/kg) did not modify social contact or preference on its own, and the A2A antagonist MSX-3 (1.5-6 mg/kg) increased social interaction at all doses. Ethanol at intermediate doses (0.5-1.0 g/kg) was able to reverse the reduction in social exploration induced by caffeine (15.0-30.0 mg/kg). Although there was no interaction between ethanol and CPT or MSX-3 on social exploration in the first day, MSX-3 blocked the amnestic effects of ethanol observed on the following day. Thus, ethanol impairs the formation of social memories, and A2A adenosine antagonists can prevent the amnestic effects of ethanol, so that animals can recognice familiar conspecifics. On the other hand, ethanol can counteract the social withdrawal induced by caffeine, a non-selective adenosine A1/A2A receptor antagonist. These results show the complex set of interactions between ethanol and caffeine, some of which could be the

Ethanol and caffeine are frequently consumed in combination and have opposite effects on the adenosine system: ethanol metabolism leads to an increase in adenosine levels, while caffeine is a non-selective adenosine A1/A2A receptor antagonist. These receptors are highly expressed in striatum and olfactory tubercle, brain areas involved in exploration and social interaction in rodents. Ethanol modulates social interaction processes, but the role of adenosine in social behavior is still poorly understood. The present work was undertaken to study the impact of ethanol, caffeine and their combination on social behavior, and to explore the involvement of A1 and A2A receptors on those actions. Male CD1 mice were evaluated in a social interaction three-chamber paradigm, for preference of conspecific vs. object, and also for long-term recognition memory of familiar vs. novel conspecific. Ethanol showed a biphasic effect, with low doses (0.25 g/kg) increasing social contact and higher doses (1.0–1.5 g/kg) reducing social interaction. However, no dose changed social preference; mice always spent more time sniffing the conspecific than the object, independently of the ethanol dose. Ethanol, even at doses that did not change social exploration, produced amnestic effects on social recognition the following day. Caffeine reduced social contact (15.0–60.0 mg/kg), and even blocked social preference at higher doses (30.0–60.0 mg/kg). The A1 antagonist Cyclopentyltheophylline (CPT; 3–9 mg/kg) did not modify social contact or preference on its own, and the A2A antagonist MSX-3 (1.5–6 mg/kg) increased social interaction at all doses. Ethanol at intermediate doses (0.5–1.0 g/kg) was able to reverse the reduction in social exploration induced by caffeine (15.0–30.0 mg/kg). Although there was no interaction between ethanol and CPT or MSX-3 on social exploration in the first day, MSX-3 blocked the amnestic effects of ethanol observed on the following day. Thus, ethanol impairs the formation of social memories, and A2A adenosine antagonists can prevent the amnestic effects of ethanol, so that animals can recognize familiar conspecifics. On the other hand, ethanol can counteract the social withdrawal induced by caffeine, a non-selective adenosine A1/A2A receptor antagonist. These results show the complex set of interactions between ethanol and caffeine, some of which could be the result of the opposing effects they have in modulating the adenosine system. [ABSTRACT FROM AUTHOR]

Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disorder, a major subset of which is characterized by the accumulation of abnormal forms of the protein tau, leading to impairments in motor functions as well as language and behavioral alterations. Tau58-2/B mice express human tau with the P301S mutation found in familial forms of FTLD in neurons. By assessing three age cohorts of Tau58-2/B mice in a comprehensive behavioral test battery, we found that the tauopathy animals showed age-dependent signs of impulsivity, decreased social exploration and executive dysfunction. The deficit in executive function was first limited to decreased spatial working memory, but with aging this was extended to impaired instrumental short-term memory. Tau pathology was prominent in brain regions underlying these behaviors. Thus, Tau-58-2/B mice recapitulate neurological deficits of the behavioral variant of frontotemporal dementia (bvFTD), presenting them as a suitable model to test therapeutic interventions for the amelioration of this variant. [ABSTRACT FROM AUTHOR]

Selective serotonin reuptake inhibitors (SSRI) are commonly prescribed antidepressant drugs in pregnant women. SSRIs cross the placental barrier and affect serotonergic neurotransmission in the fetus. Although no gross SSRI-related teratogenic effects were reported, infants born following prenatal exposure to SSRIs are at higher risk for various developmental abnormalities. The aim of this study was to examine the effects of prenatal SSRI on social and maternal behavior in mice. To this end, pregnant female dams were exposed to saline or fluoxetine (FLX) throughout pregnancy, and the behavior of the offspring was examined. The results indicate that in utero FLX increased aggression in adult males and delayed emergence of maternal behavior in adult females. Social exploration and recognition memory were not affected by prenatal FLX exposure. These findings support the notion that alterations in the development of serotonergic pathways following prenatal exposure to SSRIs are associated with changes in social and maternal behavior throughout life. [ABSTRACT FROM AUTHOR]

We recently demonstrated that acute and chronic intracerebroventricular enhancement of brain OXT levels induces potent anti-aggressive and pro-social explorative effects during social challenges. However, the exact anatomical location in the brain where OXT exerts its action is still elusive. In the present study, we targeted two critical brain areas, i.e. the central amygdala (CeA) and the dorsal raphe (DR), both containing high levels of OXT receptors (OXTRs) and constituting important nodes of the neural circuitry related to aggression. Behavioral effects of local micro-infusion of OXT and OXTR antagonist, L368.899, (alone and combined) were evaluated in resident male rats during confrontations with an unfamiliar male intruder. Our results show that OXT microinjected into the CeA markedly reduced resident's offensive behavior and facilitated social exploration, without affecting other non-aggressive behaviors. The receptor specificity of the behavioral effects was verified when a micro-infusion of a selective OXTR antagonist nullified the changes. Pharmacological blockade of CeA OXTRs per se was without clear behavioral effects suggesting that endogenous OXT within the CeA does not play a major inhibitory role on offensiveness. Anatomical specificity was also supported by the absence of relevant behavioral effects when OXT was microinjected into more medial sub-regions of the amygdala. Likewise, within the DR neither OXT nor OXTR exerted significant effects on offensive aggression, while microinjection of the 5-HT 1A autoreceptor agonist in this region significantly suppressed aggression. In conclusion, our results point at the CeA as an important brain site of action for the anti-aggressive and pro-social explorative effects induced by exogenous enhancement of brain OXT levels. [ABSTRACT FROM AUTHOR]

Summary Socio-emotional deficits and impulsive/aggressive outbursts are prevalent symptoms of many neuropsychiatric disorders, and intranasal administration of oxytocin (OXT) is emerging as a putative novel therapeutic approach to curb these problems. Recently, we demonstrated potent anti-aggressive and pro-social effects of intracerebroventricular (icv) OXT administration in male rats. The present study tested whether similar behavioral effects are induced when OXT is delivered intranasally. Heart-rate and blood-pressure responses were telemetrically monitored to investigate whether peripheral physiological effects were provoked after intranasal OXT administration. Intranasal OXT administration in resident animals reduced offensive aggression and increased social exploration toward an unfamiliar male intruder. Using a partner-preference test, intranasal OXT also strengthened the bonding between the male resident and its female partner. No changes in cardiovascular (re)activity were found, indicating an absence of direct peripheral physiological effects after intranasal OXT treatment. In conclusion, although the precise route and mechanisms of nose-to-brain transport/communication remain to be elucidated, our data demonstrated intranasal OXT to be an effective application method for suppressing intermale aggression and enhancing social affiliation. [ABSTRACT FROM AUTHOR]

Rationale: A substantial body of research suggests that the neuropeptide oxytocin promotes social affiliative behaviors in a wide range of animals including humans. However, its antiaggressive action has not been unequivocally demonstrated in male laboratory rodents. Objective: Our primary goal was to examine the putative serenic effect of oxytocin in a feral strain (wild type Groningen, WTG) of rats that generally show a much broader variation and higher levels of intermale aggression than commonly used laboratory strains of rats. Methods: Resident animals were intracerebroventricularly (icv) administered with different doses of synthetic oxytocin and oxytocin receptor antagonist, alone and in combination, in order to manipulate brain oxytocin functioning and to assess their behavioral response to an intruder. Results: Our data clearly demonstrate that acute icv administered oxytocin produces dose-dependent and receptor-selective changes in social behavior, reducing aggression and potentiating social exploration. These antiaggressive effects are stronger in the more offensive rats. On the other hand, administration of an oxytocin receptor antagonist tends to increase (nonsignificantly) aggression only in low-medium aggressive animals. Conclusions: These results suggest that transiently enhancing brain oxytocin function has potent antiaggressive effects, whereas its attenuation tends to enhance aggressiveness. In addition, a possible inverse relationship between trait aggression and endogenous oxytocinergic signaling is revealed. Overall, this study emphasizes the importance of brain oxytocinergic signaling for regulating intermale offensive aggression. This study supports the suggestion that oxytocin receptor agonists could clinically be useful for curbing heightened aggression seen in a range of neuropsychiatric disorders like antisocial personality disorder, autism, and addiction. [ABSTRACT FROM AUTHOR]

Summary: Exposure to traumatic stressors typically causes lasting changes in emotionality and behavior. However, coping strategies have been shown to prevent and alleviate many stress consequences and the biological mechanisms that underlie coping are of great interest. Whereas the laboratory stressor inescapable tail-shock induces anxiety-like behaviors, here we demonstrate that permitting a rat to chew on a wooden dowel during administration of tail-shock prevented the development of anxiety like behaviors in the open field and juvenile social exploration tests. Uncontrollable stressors increase corticosterone and decrease thyroid hormone, and we hypothesized that coping would blunt these changes. While tail-shock did produce these effects, active coping did not alter hormone levels. The dissociation between behavioral resilience and circulating hormones is discussed with regard to the utility of these molecules as biomarkers for psychiatric disease. [ABSTRACT FROM AUTHOR]

Abstract: Humans who exercise are less likely to suffer from stress-related mood disorders. Similarly, rats allowed voluntary access to running wheels have constrained corticosterone responses to mild stressors and are protected against several behavioral consequences of uncontrollable stress which resemble symptoms of human anxiety and depression, including exaggerated fear and deficits in shuttle box escape learning. Although exercise conveys clear stress resistance, the duration of time the protective effects of exercise against the behavioral consequences of uncontrollable stress persist following exercise cessation is unknown. The current studies investigated (1) whether exercise-induced stress resistance extends to social avoidance, another anxiety-like behavior elicited by uncontrollable stressor exposure, and (2) the duration of time the protective effects of exercise persist following forced cessation of exercise. Six weeks of wheel running constrained the increase in corticosterone elicited by social exploration testing, and prevented the reduction in social exploration, exaggerated shock-elicited fear, and deficits in escape learning produced by uncontrollable stress. The protective effect of voluntary exercise against stress-induced interference with escape learning persisted for 15 days, but was lost by 25 days, following cessation of exercise. An anxiogenic effect, as revealed by a reduction in social exploration and an increase in fear behavior immerged as a function of time following cessation of exercise. Results demonstrate that the protective effect of voluntary exercise against the behavioral consequences of uncontrollable stress extends to include social avoidance, and can persist for several days following exercise cessation despite an increase in anxiety produced by forced cessation of exercise. [Copyright &y& Elsevier]

Abstract: Use of individually ventilated caging (IVC) systems for mouse-based laboratory investigation has dramatically increased. We found that without mice present, intra-cage oxygen concentration was comparable (21%) between IVC housing and ambient environment caging (AEC) that used wire top lids. However, when mice were housed 4-to-a-cage for 1week, intra-cage oxygen dropped to 20.5% in IVC housing as compared to 21% for AEC housing. IVC intra-cage humidity was also elevated relative to AEC housing. Mice raised in IVC housing as compared to mice raised in AEC housing had higher RBC mass, hematocrit and hemoglobin concentrations. They also had elevated platelet counts but lower white blood cell counts. IVC mice, relative to AEC mice, had increased saccharin preference and increased fluid consumption but similar locomotion, food intake, social exploration and novel object recognition when tested in an AEC environment. Taken together, these data indicate that ventilated caging systems can have a 0.5% reduction from ambient oxygen concentration that is coupled to mouse red blood cell indices indicative of chronic exposure to a hypoxia. Importantly, IVC housing can impact behavioral testing for depressive-like behavior. [Copyright &y& Elsevier]

Jamie Oliver's celebrity image has undergone various transformations since his debut as 'the naked chef'. In this article, we focus on his recent series, Jamie's Ministry of Food, locating it within debates about lifestyle television, class and neoliberalism. We identify a shift in his image from lifestyle expert to moral entrepreneur, involved with a range of social enterprises. We examine the show's textual strategies, highlighting similarities with earlier forms of social exploration and contemporary depictions of the working class. We conclude with a consideration of how the show resonates with an emergent discourse that represents Britain as a broken society in need of political and social 'healing'. In the show, representations of fast food, obese bodies, sink estates and poverty of aspiration delineated a general crisis demanding direct action by an inspirational figure. In this way, the show legitimated Jamie's new role as a moral and social entrepreneur. [ABSTRACT FROM AUTHOR]

Background: Exposure to uncontrollable stressors often increases anxiety-like behavior in both humans and rodents. In rat, this effect depends on stress-induced activity within the dorsal raphe nucleus (DRN). However, the role of serotonin in DRN projection regions is largely unknown. The goals of this study were to 1) assess the effect of uncontrollable stress on extracellular serotonin in the basolateral amygdala during the anxiety test, 2) determine whether DRN activity during a poststress anxiety test is involved in anxiety-like behavior, and 3) determine the role of the serotonin 2C receptor (5-HT2C) in uncontrollable stress-induced anxiety. Method: Rats were exposed to tail shocks that were either controllable or uncontrollable. On the following day, anxiety-like behavior was assessed in a Juvenile Social Exploration (JSE) test. Basolateral amygdala (BLA) extracellular serotonin concentrations were assessed during JSE by in vivo microdialysis 24 hours after uncontrollable stress, controllable stress, or no stress. In separate experiments, drugs were administered before the JSE test to inhibit the DRN or to block 5-HT2C receptors. Results: Exposure to uncontrollable shock reduced later social exploration. Prior uncontrollable stress potentiated serotonin efflux in the BLA during social exploration, but controllable stress did not. Intra-DRN 8-OH-DPAT and systemic and intra-BLA 5-HT2C receptor antagonist SB 242,084 prevented the expression of potentiated anxiety in uncontrollably stressed rats. Intra-BLA injection of the 5-HT2C agonist CP 809,101 mimicked the effect of stress. Conclusions: These results suggest that the anxiety-like behavior observed after uncontrollable stress is mediated by exaggerated 5-HT acting at BLA 5-HT2C receptors. [Copyright &y& Elsevier]

The presence of behavioral control over a stressor can blunt many of the effects of the stressor. We have recently reported that uncontrollable stress (inescapable electric tailshock, IS) reduces later social exploration of a juvenile whereas controllable stress (escapable shock, ES) does not. Activation of the ventral medial prefrontal cortex (vmPFC) is crucial to blunting the effects of IS on later escape behavior (learned helplessness). The goal of the current study was to test the role of the vmPFC in modulating the effects of stressor controllability on anxiety in the social exploration test. Thus, adult male rats were implanted with cannula guides for drug microinjection into the vmPFC. In Experiment 1, temporary inactivation of the vmPFC with the GABAA agonist muscimol before exposure to ES prevented the protective effects of stress control, leading to reduced social exploration. In Experiment 2, excitation of the vmPFC prior to IS with the GABA-activated Cl( - ) channel antagonist picrotoxin mimicked the stress resistance produced by control and prevented IS-induced reduction in social exploration. These results are consistent with prior work and identify the vmPFC as a critical component of the neural circuitry mediating the effects of stressor control on later behaviors. The relationship between the vmPFC, dorsal raphe nucleus, and other structures mediating stress-induced anxiety are discussed. [ABSTRACT FROM AUTHOR]

During the course of an infection, the pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) acts in the brain to trigger development of behavioral responses, collectively termed sickness behavior. Biological activities of TNFα can be mediated by TNF receptor type 1 (TNF-R1) and type 2 (TNF-R2). TNFα activates neutral sphingomyelinase through the TNF-R1 adapter protein FAN (factor associated with neutral sphingomyelinase activation), but a behavioral role of FAN in the brain has never been reported. We hypothesized that TNFα-induced sickness behavior requires TNF-R1 and that FAN is a necessary component for this response. We determined the role of brain TNF-R1 in sickness behavior by administering an optimal amount of TNFα intracerebroventricularly (i.c.v., 50 ng/mouse) to wild-type (WT), TNF-R1-, TNF-R2-, and FAN-deficient mice. Sickness was assessed by decreased social exploration of a novel juvenile, induction of immobility, and loss of body weight. TNF-R1-deficient mice were resistant to the sickness-inducing properties of i.c.v. TNFα, whereas both TNF-R2-deficient and WT mice were fully responsive. Furthermore, the complete absence of TNFα-induced sickness behavior in FAN-deficient mice provided in vivo evidence that FAN-dependent TNF-R1 signaling is critical for this central action of TNFα. This is the first report to demonstrate that TNFα-induced sickness behavior is fully mediated by TNF-R1 and that the adaptor protein FAN is a necessary intracellular intermediate for sickness behavior. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor-α (TNFα) acts within the brain to induce sickness behavior, but the molecular mechanisms are still unknown. TNFα binding induces receptor trimerization, activation of c-Jun N-terminal kinase (JNK), and induction of downstream transcription factors. We hypothesized that TNFα-induced sickness behavior can be blocked by a novel JNK inhibitor. To test this idea, we used a bipartite protein consisting of a ten-amino-acid sequence of the trans-activating domain of the viral TAT protein (D-TAT) linked to a 19-amino-acid peptide that specifically inhibits JNK activation (D-JNKI-1). C57BL/6J mice were pre-treated intracerebroventricularly (i.c.v.) with D-JNKI-1 or the control peptide containing only the protein transduction domain, D-TAT. Mice were then injected centrally with an optimal amount of TNFα (50 ng/mouse) to induce sickness behavior. Sickness was assessed as a decrease in social exploration of a novel juvenile, an increase in duration of immobility and loss of body weight. Pre-treatment with D-JNKI-1 (10 ng/mouse), but not D-TAT, significantly inhibited all three indices of sickness induced by central TNFα. These findings demonstrate that D-JNKI-1 can abrogate TNFα-induced sickness behavior and suggest a potential therapeutic target for treating major depressive disorders that develop on a background of cytokine-induced sickness behavior. [ABSTRACT FROM AUTHOR]

Summary: Both early-life stress and immune system activation in adulthood have been linked independently to depression in a number of studies. However, the relationship between early-life infection, which may be considered a “stressor”, and later-life depression has not been explored. We have reported that neonatal bacterial infection in rats leads to exaggerated brain cytokine production, as well as memory impairments, to a subsequent peripheral immune challenge in adulthood, and therefore predicted that stressor-induced depressive-like symptoms would be more severe in these rats as well. Rats treated on postnatal day 4 with PBS or Escherichia coli were as adults exposed to inescapable tailshock stress (IS), and then tested for sucrose preference, social exploration with a juvenile, and overall activity, 1, 3, 5, and 7 days following the stressor. Serum corticosterone and extracellular 5-HT within the basolateral amygdala were measured in a second group of rats in response to the IS. IS resulted in profound depressive-like behaviors in adult rats, but, surprisingly, rats that suffered a bacterial infection early in life had blunted corticosterone responses to the stressor and were remarkably protected from the depressive symptoms compared to controls. These data suggest that early-life infection should be considered within a cost/benefit perspective, in which outcomes in adulthood may be differentially protected or impaired. These data also suggest that the immune system likely plays a previously unsuspected role in “homeostatic” HPA programming and brain development, which may ultimately lend insight into the often-contradictory literature on cytokines, inflammation, and depression. [Copyright &y& Elsevier]

Abstract: We have previously shown that type 2 diabetes (T2D) in the mouse is associated with increased responsivity to innate immune challenge. Here we demonstrate that in a mouse model of type 1 diabetes (T1D) LPS-dependent suppression of social exploration (SE) is augmented and dependent on hyperglycemia. T1D was induced in mice with intraperitoneal (i.p.) streptozotocin (STZ). After 4d, STZ treated mice had blood glucose levels of 417±34mg/dl compared to 160±11mg/dl in non-STZ treated mice. When these diabetic mice were challenged with i.p. lipopolysaccharide (LPS), LPS-induced depression of SE was nearly 2.7-fold greater in diabetic mice at 2h than in non-diabetic mice. Examination of peritoneal proinflammatory cytokine levels 2h after LPS administration showed that diabetic mice had 4-, 2.5- and 3.6-fold greater concentrations of IL-1β, IL-6 and TNF-α, respectively, when compared to non-diabetic mice. Control of blood glucose levels with injected insulin in diabetic mice improved 2h post LPS-induced loss of SE by 3.9-fold. Interestingly, insulin given intracerebroventricularly to diabetic mice did not impact LPS-induced loss of SE but did increase basal SE 8, 12 and 24h later. Finally, administration of STZ to hyperglycemic/hyperinsulinemic db/db mice did not alter LPS-induced loss of SE. Taken together these findings indicate that mice with T1D have augmented loss of SE in response to LPS and this is due to hyperglycemia and not to insulin. [Copyright &y& Elsevier]

Abstract: Cytokine-induced sickness behavior was recognized within a few years of the cloning and expression of interferon-α, IL-1 and IL-2, which occurred around the time that the first issue of Brain, Behavior, and Immunity was published in 1987. Phase I clinical trials established that injection of recombinant cytokines into cancer patients led to a variety of psychological disturbances. It was subsequently shown that physiological concentrations of proinflammatory cytokines that occur after infection act in the brain to induce common symptoms of sickness, such as loss of appetite, sleepiness, withdrawal from normal social activities, fever, aching joints and fatigue. This syndrome was defined as sickness behavior and is now recognized to be part of a motivational system that reorganizes the organism’s priorities to facilitate recovery from the infection. Cytokines convey to the brain that an infection has occurred in the periphery, and this action of cytokines can occur via the traditional endocrine route via the blood or by direct neural transmission via the afferent vagus nerve. The finding that sickness behavior occurs in all mammals and birds indicates that communication between the immune system and brain has been evolutionarily conserved and forms an important physiological adaptive response that favors survival of the organism during infections. The fact that cytokines act in the brain to induce physiological adaptations that promote survival has led to the hypothesis that inappropriate, prolonged activation of the innate immune system may be involved in a number of pathological disturbances in the brain, ranging from Alzheimer’s disease to stroke. Conversely, the newly-defined role of cytokines in a wide variety of systemic co-morbid conditions, ranging from chronic heart failure to obesity, may begin to explain changes in the mental state of these subjects. Indeed, the newest findings of cytokine actions in the brain offer some of the first clues about the pathophysiology of certain mental health disorders, including depression. The time is ripe to begin to move these fundamental discoveries in mice to man and some of the pharmacological tools are already available to antagonize the detrimental actions of cytokines. [Copyright &y& Elsevier]

Systemic administration of bacterial lipopolysaccharide (LPS) induces a series of physiological and pathological alterations as well as behavioral depression in experimental animals. These alterations induced by LPS administration are known to be mediated by endogenous cytokines and arachidonate metabolites, which may be modulated by dietary n-3 fatty acids. Mice were fed a diet supplemented with n-3 or n-6 fatty acids for 4 weeks prior to LPS administration. Food-motivated behavior after intraperitoneal administration of LPS as compared with that before LPS administration was significantly depressed in the mice fed with the n-6 fatty-acid-rich diet (47% to 85% reduction; P<.05) but not significantly in the mice fed with the n-3 fatty-acid-rich diet. Depression of social exploration by intraperitoneal LPS administration in the n-3 fatty-acid-rich diet group (39% reduction vs. vehicle group) was significantly less in the n-6 fatty-acid-rich diet group (76% reduction vs. vehicle group; P<.05). The behavioral depressions induced by intracerebroventricular LPS injection were not significantly different between the two dietary groups (P=.60). The elevation of serum corticosterone and the hypoglycemic response following intraperitoneal LPS administration were not significantly different between the two dietary groups (P=.57 and P=.43, respectively). We demonstrate that dietary n-3 fatty acids attenuate behavioral depression in mice peripherally administered with LPS without affecting the increase in serum corticosterone and the decrease in serum glucose concentration. [Copyright &y& Elsevier]

In two lines of White Leghorns that differ in their propensity to feather peck, feather pecking was already present 1 day after hatching. A significant line difference developed within 3 days and this difference remained in the following weeks. There was no clear relationship between feather pecking and ground pecking, instead feather pecking was associated with other socially orientated pecks. When chicks were confronted with feathers as an inanimate stimulus pecking at these feathers did not reflect pecking in a social context. These results suggest that feather pecking has an underlying social component, rather than being a redirected behaviour. To test the influence of social factors on feather pecking, chicks from the high feather pecking line were subjected to regular rehousing or regular rehousing plus confrontation with unfamiliar peers. Gentle feather pecking increased significantly in groups that were rehoused with unfamiliar peers. Directly after confrontation chicks displayed a preference in the total number of pecks toward these unfamiliar birds. Gentle feather pecking as a separate pecking orientation showed a similar trend. Increased righting times in a tonic immobility test were recorded in the experimental groups, hence frequent confrontation with unfamiliar peers may be experienced by chicks as stressful, which is consistent with the hypothesis that stress mediates the expression of feather pecking. In contrast to the dominant hypotheses in the field, we argue that gentle feather pecking at an early age plays an important role in the building (social exploration) and maintenance of social relationships between chicks. [Copyright &y& Elsevier]