Adrenalectomy prevents the effects of social defeat stress on PER2 rhythms in some peripheral tissues in male mice.

While stress does not affect the phase or period of the central pacemaker in the suprachiasmatic nucleus, it can shift clocks in peripheral tissues. Our previous studies showed significant delays of the PER2 rhythms in lung and kidney following social defeat stress. The mechanism underlying these effects is not fully understood, but might involve glucocorticoids (GC) released during the stressor. In the present study, we performed social defeat stress in adrenalectomized (ADX) mice to see if the induction of endogenous GC is necessary for the stress-induced phase shifts of peripheral clocks. We used mice that carry a luciferase reporter gene fused to the circadian clock gene Period2 (PER2::LUC) to examine daily rhythms of PER2 expression in various peripheral tissues. Mice were exposed to 5 consecutive daily social defeat stress in the late dark phase (ZT21-22). Running wheel rotations were recorded during 7 baseline and 5 social defeat days, which showed that social defeat stress suppressed locomotor activity without affecting the phase of the rhythm. This suppression of activity was not prevented by ADX. One hour after the last stressor, tissue samples from the liver, kidney and lung were collected and cultured for ex vivo bioluminescence recordings. In the liver, PER2 rhythms were not affected by social defeat stress or ADX. In the kidney, social defeat stress caused a > 4 h phase delay of the PER2 rhythm, which was prevented by ADX, supporting the hypothesis of a crucial role of GC in this stress effect. In the lung, social defeat stress caused an 8 h phase delay, but, surprisingly, a similar phase delay was seen in ADX animals independent of defeat. The latter indicates complex effects of stress and stress hormones on the lung clock. In conclusion, the findings show that repeated social defeat stress in the dark phase can shift PER2 rhythms in some tissues (lung, kidney) and not others (liver). Moreover, the social defeat stress effect in some tissues appears to be mediated by glucocorticoids (kidney) whereas the mechanism in other tissues is more complex (lung).

The impact of stress and stress hormones on endogenous clocks and circadian rhythms.

In mammals, daily rhythms in physiology and behavior are under control of a circadian pacemaker situated in the suprachiasmatic nucleus (SCN). This master clock receives photic input from the retina and coordinates peripheral oscillators present in other tissues, maintaining all rhythms in the body synchronized to the environmental light-dark cycle. In line with its function as a master clock, the SCN appears to be well protected against unpredictable stressful stimuli. However, available data indicate that stress and stress hormones at certain times of day are capable of shifting peripheral oscillators in, e.g., liver, kidney and heart, which are normally under control of the SCN. Such shifts of peripheral oscillators may represent a temporary change in circadian organization that facilitates adaptation to repeated stress. Alternatively, these shifts of internal rhythms may represent an imbalance between precisely orchestrated physiological and behavioral processes that may have severe consequences for health and well-being.

Seasonal variation in rest-activity patterns in barnacle geese: are measurements of activity a good indicator of sleep-wake patterns?

Sleep is a widely spread phenomenon in the animal kingdom and is thought to serve important functions. Yet, the function of sleep remains an enigma. Studies in non-model animal species in their natural habitat might provide more insight into the evolution and function of sleep. However, polysomnography in the wild may not always be an option or first choice and some studies may need to rely on rest-activity recordings as a proxy for sleep and wakefulness. In the current paper, we analyzed how accelerometry-based activity data correlate with electroencephalogram (EEG)-based sleep-wake patterns in barnacle geese under seminatural conditions across different seasons. In winter, the geese had pronounced daily rhythms in rest and activity, with most activity occurring during the daytime. In summer, activity was more spread out over the 24 h cycle. Hourly activity scores strongly correlated with EEG-determined time awake, but the strength of the correlation varied with phase of the day and season. In winter, the correlations between activity and waking time were weaker for daytime than for night-time. Furthermore, the correlations between activity and waking during daytime were weaker in winter than in summer. During daytime in winter, there were many instances where the birds were awake but not moving. Experimental sleep deprivation had no effect on the strength of the correlation between activity scores and EEG-based wake time. Overall, hourly activity scores also showed significant inverse correlation with the time spent in non-rapid eye movement (NREM) sleep. However, correlation between activity scores and time spent in REM sleep was weak. In conclusion, accelerometry-based activity scores can serve as a good estimate for time awake or even the specific time spent in NREM sleep. However, activity scores cannot reliably predict REM sleep and sleep architecture.

Sleep deprivation reduces the density of individual spine subtypes in a branch-specific fashion in CA1 neurons.

Sleep deprivation has a negative impact on hippocampus-dependent memory, which is thought to depend on cellular plasticity. We previously found that 5 h of sleep deprivation robustly decreases dendritic spine density in the CA1 area of the hippocampus in adult male mice. However, recent work by others suggests that sleep deprivation increases the density of certain spine types on specific dendritic branches. Based on these recent findings and our previous work, we conducted a more in-depth analysis of different spine types on branches 1, 2 and 5 of both apical and basal dendrites to assess whether 5 h of sleep deprivation may have previously unrecognized spine-type and branch-specific effects. This analysis shows no spine-type specific changes on branch 1 and 2 of apical dendrites after sleep deprivation. In contrast, sleep deprivation decreases the number of mushroom and branched spines on branch 5. Likewise, sleep deprivation reduces thin, mushroom and filopodia spine density on branch 5 of the basal dendrites, without affecting spines on branch 1 and 2. Our findings indicate that sleep deprivation leads to local branch-specific reduction in the density of individual spine types, and that local effects might not reflect the overall impact of sleep deprivation on CA1 structural plasticity. Moreover, our analysis underscores that focusing on a subset of dendritic branches may lead to potential misinterpretation of the overall impact of, in this case, sleep deprivation on structural plasticity.

A comparison of continuous and intermittent EEG recordings in geese: How much data are needed to reliably estimate sleep-wake patterns?

Recent technological advancements allow researchers to measure electrophysiological parameters of animals, such as sleep, in remote locations by using miniature dataloggers. Yet, continuous recording of sleep might be constrained by the memory and battery capacity of the recording devices. These limitations can be alleviated by recording intermittently instead of continuously, distributing the limited recording capacity over a longer period. We assessed how reduced sampling of sleep recordings affected measurement precision of NREM sleep, REM sleep, and Wake. We analysed a dataset on sleep in barnacle geese that we resampled following 12 different recording schemes, with data collected for 1 min per 5 min up to 1 min per 60 min in steps of 5 min. Recording 1 min in 5 min still yielded precise estimates of hourly sleep-wake values (correlations of 0.9) while potentially extending the total recording period by a factor of 5. The correlation strength gradually decreased to 0.5 when recording 1 min per 60 min. For hourly values of Wake and NREM sleep, the correlation strength in winter was higher compared with summer, reflecting more fragmented sleep in summer. Interestingly for hourly values of REM sleep, correlations were unaffected by season. Estimates of total 24 h sleep-wake values were similar for all intermittent recording schedules compared to the continuous recording. These data indicate that there is a large safe range in which researchers can periodically record sleep. Increasing the sample size while maintaining precision can substantially increase the statistical power, and is therefore recommended whenever the total recording time is limited.

Elucidating the role of protein synthesis in hippocampus-dependent memory consolidation across the day and night.

It is widely acknowledged that de novo protein synthesis is crucial for the formation and consolidation of long-term memories. While the basal activity of many signaling cascades that modulate protein synthesis fluctuates in a circadian fashion, it is unclear whether the temporal dynamics of protein synthesis-dependent memory consolidation vary depending on the time of day. More specifically, it is unclear whether protein synthesis inhibition affects hippocampus-dependent memory consolidation in rodents differentially across the day (i.e., the inactive phase with an abundance of sleep) and night (i.e., the active phase with little sleep). To address this question, male and female C57Bl6/J mice were trained in a contextual fear conditioning task at the beginning or the end of the light phase. Animals received a single systemic injection with the protein synthesis inhibitor anisomycin or vehicle directly, 4, 8 hr, or 11.5 hr following training, and memory was assessed after 24 hr. Here, we show that protein synthesis inhibition impaired the consolidation of context-fear memories selectively when the protein synthesis inhibitor was administered at the first three time points, irrespective of timing of training. Even though the basal activity of signaling pathways regulating de novo protein synthesis may fluctuate across the 24-hr cycle, these results suggest that the temporal dynamics of protein synthesis-dependent memory consolidation are similar for day-time and night-time learning.

A brief period of sleep deprivation negatively impacts the acquisition, consolidation, and retrieval of object-location memories.

Memory is a cognitive concept and refers to the storage of information over a longer time period. It exists of a series of complementary processes; acquisition, consolidation, and retrieval. Each of these processes has its own partly unique neurobiological signature. Sleep deprivation is known to impair hippocampus-dependent long-term memories. Many studies have used extended periods of wakefulness, affecting all three memory processes, thereby making it unable to determine how each of the processes is affected by sleep loss, separately. Others have extensively examined the effects on memory consolidation, showing the detrimental effect of sleep deprivation during the consolidation process on memory formation. Few studies have investigated how memory acquisition and its retrieval are affected by sleep loss. In the present study, we therefore assessed in mice how sleep deprivation negatively impacts memory acquisition, consolidation, and retrieval, in the Object Location Memory task. Mice were sleep deprived for six hours at the beginning of the light phase using the gentle handling method, 1) directly preceding the learning trial (acquisition), 2) immediately after the learning trial (consolidation), or 3) directly preceding the test trial (retrieval). Memory was assessed at either a 24-h or 1-h interval. Using this approach, we show for the first time that six hours of sleep deprivation attenuates the acquisition, consolidation, and retrieval of object-location memories in mice.

Phosphodiesterase inhibitors roflumilast and vardenafil prevent sleep deprivation-induced deficits in spatial pattern separation.

Sleep deprivation (SD) is known to impair hippocampus-dependent memory processes, in part by stimulating the phosphodiesterase (PDE) activity. In the present study, we assessed in mice whether SD also affects spatial pattern separation, a cognitive process that specifically requires the dentate gyrus (DG) subregion of the hippocampus. Adult male mice were trained in an object pattern separation (OPS) task in the middle of the light phase and then tested 24 hr thereafter. In total, we conducted three studies using the OPS task. In the first study, we validated the occurrence of pattern separation and tested the effects of SD. We found that 6 hr of SD during the first half of the light phase directly preceding the test trial impaired the spatial pattern separation performance. As a next step, we assessed in two consecutive studies whether the observed SD-induced performance deficits could be prevented by the systemic application of two different PDE inhibitors that are approved for human use. Both the PDE4 inhibitor roflumilast and PDE5 inhibitor vardenafil successfully prevented SD-induced deficits in spatial pattern separation. As a result, these PDE inhibitors have clinical potential for the prevention of memory deficits associated with loss of sleep.

Sleep deprivation-induced impairment of memory consolidation is not mediated by glucocorticoid stress hormones.

The general consensus is that sleep promotes neuronal recovery and plasticity, whereas sleep deprivation (SD) impairs brain function, including cognitive processes. Indeed, a wealth of data has shown a negative impact of SD on learning and memory processes, particularly those that involve the hippocampus. The mechanisms underlying these negative effects of sleep loss are only partly understood, but a reoccurring question is whether they are in part caused by stress hormones that may be released during SD. The purpose of the present study is therefore to examine the role of glucocorticoid stress hormones in SD-induced memory impairment. Male C57BL/6J mice were trained in an object-location memory paradigm, followed by 6 hr of SD by mild stimulation. At the beginning of the SD mice were injected with the corticosterone synthesis inhibitor metyrapone. Memory was tested 24 hr after training. Blood samples taken in a separate group of mice showed that SD resulted in a mild but significant increase in plasma corticosterone levels, which was prevented by metyrapone. However, the SD-induced impairment in object-location memory was not prevented by metyrapone treatment. This indicates that glucocorticoids play no role in causing the memory impairments seen after a short period of SD.

Human and rat gut microbiome composition is maintained following sleep restriction.

Insufficient sleep increasingly characterizes modern society, contributing to a host of serious medical problems. Loss of sleep is associated with metabolic diseases such as obesity and diabetes, cardiovascular disorders, and neurological and cognitive impairments. Shifts in gut microbiome composition have also been associated with the same pathologies; therefore, we hypothesized that sleep restriction may perturb the gut microbiome to contribute to a disease state. In this study, we examined the fecal microbiome by using a cross-species approach in both rat and human studies of sleep restriction. We used DNA from hypervariable regions (V1-V2) of 16S bacteria rRNA to define operational taxonomic units (OTUs) of the microbiome. Although the OTU richness of the microbiome is decreased by sleep restriction in rats, major microbial populations are not altered. Only a single OTU, TM7-3a, was found to increase with sleep restriction of rats. In the human microbiome, we find no overt changes in the richness or composition induced by sleep restriction. Together, these results suggest that the microbiome is largely resistant to changes during sleep restriction.

The preference and costs of sleeping under light at night in forest and urban great tits.

Artificial light at night (ALAN) is an increasing phenomenon associated with worldwide urbanization. In birds, broad-spectrum white ALAN can have disruptive effects on activity patterns, metabolism, stress response and immune function. There has been growing research on whether the use of alternative light spectra can reduce these negative effects, but surprisingly, there has been no study to determine which light spectrum birds prefer. To test such a preference, we gave urban and forest great tits (Parus major) the choice where to roost using pairwise combinations of darkness, white light or green dim light at night (1.5 lux). Birds preferred to sleep under artificial light instead of darkness, and green was preferred over white light. In a subsequent experiment, we investigated the consequence of sleeping under a particular light condition, and measured birds' daily activity levels, daily energy expenditure (DEE), oxalic acid as a biomarker for sleep debt and cognitive abilities. White light affected activity patterns more than green light. Moreover, there was an origin-dependent response to spectral composition: in urban birds, the total daily activity and night activity did not differ between white and green light, while forest birds were more active under white than green light. We also found that individuals who slept under white and green light had higher DEE. However, there were no differences in oxalic acid levels or cognitive abilities between light treatments. Thus, we argue that in naive birds that had never encountered light at night, white light might disrupt circadian rhythms more than green light. However, it is possible that the negative effects of ALAN on sleep and cognition might be observed only under intensities higher than 1.5 lux. These results suggest that reducing the intensity of light pollution as well as tuning the spectrum towards long wavelengths may considerably reduce its impact.

A brief period of sleep deprivation causes spine loss in the dentate gyrus of mice.

Sleep and sleep loss have a profound impact on hippocampal function, leading to memory impairments. Modifications in the strength of synaptic connections directly influences neuronal communication, which is vital for normal brain function, as well as the processing and storage of information. In a recently published study, we found that as little as five hours of sleep deprivation impaired hippocampus-dependent memory consolidation, which was accompanied by a reduction in dendritic spine numbers in hippocampal area CA1. Surprisingly, loss of sleep did not alter the spine density of CA3 neurons. Although sleep deprivation has been reported to affect the function of the dentate gyrus, it is unclear whether a brief period of sleep deprivation impacts spine density in this region. Here, we investigated the impact of a brief period of sleep deprivation on dendritic structure in the dentate gyrus of the dorsal hippocampus. We found that five hours of sleep loss reduces spine density in the dentate gyrus with a prominent effect on branched spines. Interestingly, the inferior blade of the dentate gyrus seems to be more vulnerable in terms of spine loss than the superior blade. This decrease in spine density predominantly in the inferior blade of the dentate gyrus may contribute to the memory deficits observed after sleep loss, as structural reorganization of synaptic networks in this subregion is fundamental for cognitive processes.

Oxalic acid and diacylglycerol 36:3 are cross-species markers of sleep debt.

Sleep is an essential biological process that is thought to have a critical role in metabolic regulation. In humans, reduced sleep duration has been associated with risk for metabolic disorders, including weight gain, diabetes, obesity, and cardiovascular disease. However, our understanding of the molecular mechanisms underlying effects of sleep loss is only in its nascent stages. In this study we used rat and human models to simulate modern-day conditions of restricted sleep and addressed cross-species consequences via comprehensive metabolite profiling. Serum from sleep-restricted rats was analyzed using polar and nonpolar methods in two independent datasets (n = 10 per study, 3,380 measured features, 407 identified). A total of 38 features were changed across independent experiments, with the majority classified as lipids (18 from 28 identified). In a parallel human study, 92 metabolites were identified as potentially significant, with the majority also classified as lipids (32 of 37 identified). Intriguingly, two metabolites, oxalic acid and diacylglycerol 36:3, were robustly and quantitatively reduced in both species following sleep restriction, and recovered to near baseline levels after sleep restriction (P < 0.05, false-discovery rate < 0.2). Elevated phospholipids were also noted after sleep restriction in both species, as well as metabolites associated with an oxidizing environment. In addition, polar metabolites reflective of neurotransmitters, vitamin B3, and gut metabolism were elevated in sleep-restricted humans. These results are consistent with induction of peroxisome proliferator-activated receptors and disruptions of the circadian clock. The findings provide a potential link between known pathologies of reduced sleep duration and metabolic dysfunction, and potential biomarkers for sleep loss.

Compartmentalized PDE4A5 Signaling Impairs Hippocampal Synaptic Plasticity and Long-Term Memory.

UNLABELLED: Alterations in cAMP signaling are thought to contribute to neurocognitive and neuropsychiatric disorders. Members of the cAMP-specific phosphodiesterase 4 (PDE4) family, which contains >25 different isoforms, play a key role in determining spatial cAMP degradation so as to orchestrate compartmentalized cAMP signaling in cells. Each isoform binds to a different set of protein complexes through its unique N-terminal domain, thereby leading to targeted degradation of cAMP in specific intracellular compartments. However, the functional role of specific compartmentalized PDE4 isoforms has not been examined in vivo Here, we show that increasing protein levels of the PDE4A5 isoform in mouse hippocampal excitatory neurons impairs a long-lasting form of hippocampal synaptic plasticity and attenuates hippocampus-dependent long-term memories without affecting anxiety. In contrast, viral expression of a truncated version of PDE4A5, which lacks the unique N-terminal targeting domain, does not affect long-term memory. Further, overexpression of the PDE4A1 isoform, which targets a different subset of signalosomes, leaves memory undisturbed. Fluorescence resonance energy transfer sensor-based cAMP measurements reveal that the full-length PDE4A5, in contrast to the truncated form, hampers forskolin-mediated increases in neuronal cAMP levels. Our study indicates that the unique N-terminal localization domain of PDE4A5 is essential for the targeting of specific cAMP-dependent signaling underlying synaptic plasticity and memory. The development of compounds to disrupt the compartmentalization of individual PDE4 isoforms by targeting their unique N-terminal domains may provide a fruitful approach to prevent cognitive deficits in neuropsychiatric and neurocognitive disorders that are associated with alterations in cAMP signaling. SIGNIFICANCE STATEMENT: Neurons exhibit localized signaling processes that enable biochemical cascades to be activated selectively in specific subcellular compartments. The phosphodiesterase 4 (PDE4) family coordinates the degradation of cAMP, leading to the local attenuation of cAMP-dependent signaling pathways. Sleep deprivation leads to increased hippocampal expression of the PDE4A5 isoform. Here, we explored whether PDE4A5 overexpression mimics behavioral and synaptic plasticity phenotypes associated with sleep deprivation. Viral expression of PDE4A5 in hippocampal neurons impairs long-term potentiation and attenuates the formation of hippocampus-dependent long-term memories. Our findings suggest that PDE4A5 is a molecular constraint on cognitive processes and may contribute to the development of novel therapeutic approaches to prevent cognitive deficits in neuropsychiatric and neurocognitive disorders that are associated with alterations in cAMP signaling.

Maternal inflammation induces immune activation of fetal microglia and leads to disrupted microglia immune responses, behavior, and learning performance in adulthood.

Maternal inflammation during pregnancy can have detrimental effects on embryonic development that persist during adulthood. However, the underlying mechanisms and insights in the responsible cell types are still largely unknown. Here we report the effect of maternal inflammation on fetal microglia, the innate immune cells of the central nervous system (CNS). In mice, a challenge with LPS during late gestation stages (days 15-16-17) induced a pro-inflammatory response in fetal microglia. Adult whole brain microglia of mice that were exposed to LPS during embryonic development displayed a persistent reduction in pro-inflammatory activation in response to a re-challenge with LPS. In contrast, hippocampal microglia of these mice displayed an increased inflammatory response to an LPS re-challenge. In addition, a reduced expression of brain-derived neurotrophic factor (BDNF) was observed in hippocampal microglia of LPS-offspring. Microglia-derived BDNF has been shown to be important for learning and memory processes. In line with these observations, behavioral- and learning tasks with mice that were exposed to maternal inflammation revealed reduced home cage activity, reduced anxiety and reduced learning performance in a T-maze. These data show that exposure to maternal inflammation during late gestation results in long term changes in microglia responsiveness during adulthood, which is different in nature in hippocampus compared to total brain microglia.

Restless roosts: Light pollution affects behavior, sleep, and physiology in a free-living songbird.

The natural nighttime environment is increasingly polluted by artificial light. Several studies have linked artificial light at night to negative impacts on human health. In free-living animals, light pollution is associated with changes in circadian, reproductive, and social behavior, but whether these animals also suffer from physiologic costs remains unknown. To fill this gap, we made use of a unique network of field sites which are either completely unlit (control), or are artificially illuminated with white, green, or red light. We monitored nighttime activity of adult great tits, Parus major, and related this activity to within-individual changes in physiologic indices. Because altered nighttime activity as a result of light pollution may affect health and well-being, we measured oxalic acid concentrations as a biomarker for sleep restriction, acute phase protein concentrations and malaria infection as indices of immune function, and telomere lengths as an overall measure of metabolic costs. Compared to other treatments, individuals roosting in the white light were much more active at night. In these individuals, oxalic acid decreased over the course of the study. We also found that individuals roosting in the white light treatment had a higher probability of malaria infection. Our results indicate that white light at night increases nighttime activity levels and sleep debt and affects disease dynamics in a free-living songbird. Our study offers the first evidence of detrimental effects of light pollution on the health of free-ranging wild animals.

Sleep restriction in rats leads to changes in operant behaviour indicative of reduced prefrontal cortex function.

Sleep deprivation has profound effects on cognitive performance, and some of these effects may be mediated by impaired prefrontal cortex function. In search of an animal model to investigate this relationship we studied the influence of restricted sleep on operant conditioning in rats, particularly the performance in a differential reinforcement of low rate responding (DRL) task, which is highly dependent upon an intact prefrontal cortex. Animals were trained to withhold a lever press until an imposed delay of 30 s after the last press had passed in order to achieve a food reward. Once the animals had mastered the task, they were sleep-restricted for 7 days with 20 h of sleep deprivation per day. At the end of each daily sleep deprivation session, performance on the DRL task was assessed. The results show that sleep-restricted animals were less able to time their responses correctly, started pressing the lever more randomly and showed signs of behavioural disinhibition, the latter possibly reflecting enhanced impulsivity. Our data support the hypothesis that a sleep debt has disruptive consequences for the functioning of the prefrontal cortex. This model offers possibilities for future studies investigating the underlying biochemical and molecular mechanisms of this relationship.

Transiently increasing cAMP levels selectively in hippocampal excitatory neurons during sleep deprivation prevents memory deficits caused by sleep loss.

The hippocampus is particularly sensitive to sleep loss. Although previous work has indicated that sleep deprivation impairs hippocampal cAMP signaling, it remains to be determined whether the cognitive deficits associated with sleep deprivation are caused by attenuated cAMP signaling in the hippocampus. Further, it is unclear which cell types are responsible for the memory impairments associated with sleep deprivation. Transgenic approaches lack the spatial resolution to manipulate specific signaling pathways selectively in the hippocampus, while pharmacological strategies are limited in terms of cell-type specificity. Therefore, we used a pharmacogenetic approach based on a virus-mediated expression of a Gαs-coupled Drosophila octopamine receptor selectively in mouse hippocampal excitatory neurons in vivo. With this approach, a systemic injection with the receptor ligand octopamine leads to increased cAMP levels in this specific set of hippocampal neurons. We assessed whether transiently increasing cAMP levels during sleep deprivation prevents memory consolidation deficits associated with sleep loss in an object-location task. Five hours of total sleep deprivation directly following training impaired the formation of object-location memories. Transiently increasing cAMP levels in hippocampal neurons during the course of sleep deprivation prevented these memory consolidation deficits. These findings demonstrate that attenuated cAMP signaling in hippocampal excitatory neurons is a critical component underlying the memory deficits in hippocampus-dependent learning tasks associated with sleep deprivation.

Similar serotonin-2A receptor binding in rats with different coping styles or levels of aggression.

Individual differences in coping style emerge as a function of underlying variability in the activation of a mesocorticolimbic brain circuitry. Particularly serotonin seems to play an important role. For this reason, we assessed serotonin-2A receptor (5-HT2A R) binding in the brain of rats with different coping styles. We compared proactive and reactive males of two rat strains, Wild-type Groningen (WTG) and Roman high- and low avoidance (RHA, RLA). 5-HT2A R binding in (pre)frontal cortex (FC) and hippocampus was investigated using a radiolabeled antagonist ([(3) H]MDL-100907) and agonist ([(3) H]Cimbi-36) in binding assays. No differences in 5-HT2A R binding were observed in male animals with different coping styles. [(3) H]MDL-100907 displayed a higher specific-to-nonspecific binding ratio than [(3) H]Cimbi-36. Our findings suggest that in these particular rat strains, 5-HT2A R binding is not an important molecular marker for coping style. Because neither an antagonist nor an agonist tracer showed any binding differences, it is unlikely that the affinity state of the 5-HT2A R is co-varying with levels of aggression or active avoidance in WTG, RHA and RLA.

Deep sleep after social stress: NREM sleep slow-wave activity is enhanced in both winners and losers of a conflict.

Sleep is considered to be a recovery process of prior wakefulness. Not only duration of the waking period affects sleep architecture and sleep EEG, the quality of wakefulness is also highly important. Studies in rats have shown that social defeat stress, in which experimental animals are attacked and defeated by a dominant conspecific, is followed by an acute increase in NREM sleep EEG slow wave activity (SWA). However, it is not known whether this effect is specific for the stress of social defeat or a result of the conflict per se. In the present experiment, we examined how sleep is affected in both the winners and losers of a social conflict. Sleep-wake patterns and sleep EEG were recorded in male wild-type Groningen rats that were subjected to 1h of social conflict in the middle of the light phase. All animals were confronted with a conspecific of similar aggression level and the conflict took place in a neutral arena where both individuals had an equal chance to either win or lose the conflict. NREM sleep SWA was significantly increased after the social conflict compared to baseline values and a gentle stimulation control condition. REM sleep was significantly suppressed in the first hours after the conflict. Winners and losers did not differ significantly in NREM sleep time, NREM sleep SWA and REM sleep time immediately after the conflict. Losers tended to have slightly more NREM sleep later in the recovery period. This study shows that in rats a social conflict with an unpredictable outcome has quantitatively and qualitatively largely similar acute effects on subsequent sleep in winners and losers.