Normal Social Behavior Research Articles

Integrin \u03b23 in forebrain Emx1-expressing cells regulates repetitive self-grooming and sociability in mice

BackgroundAutism spectrum disorder (ASD) is characterized by repetitive behaviors, deficits in communication, and overall impaired social interaction. Of all the integrin subunit mutations, mutations in integrin β3 (Itgb3) may be the most closely associated with ASD. Integrin β3 is required for normal structural plasticity of dendrites and synapses specifically in excitatory cortical and hippocampal circuitry. However, the behavioral consequences of Itgb3 function in the forebrain have not been assessed. We tested the hypothesis that behaviors that are typically abnormal in ASD—such as self-grooming and sociability behaviors—are disrupted with conditional Itgb3 loss of function in forebrain circuitry in male and female mice.MethodsWe generated male and female conditional knockouts (cKO) and conditional heterozygotes (cHET) of Itgb3 in excitatory neurons and glia that were derived from Emx1-expressing forebrain cells during development. We used several different assays to determine whether male and female cKO and cHET mice have repetitive self-grooming behaviors, anxiety-like behaviors, abnormal locomotion, compulsive-like behaviors, or abnormal social behaviors, when compared to male and female wildtype (WT) mice.ResultsOur findings indicate that only self-grooming and sociability are altered in cKO, but not cHET or WT mice, suggesting that Itgb3 is specifically required in forebrain Emx1-expressing cells for normal repetitive self-grooming and social behaviors. Furthermore, in cKO (but not cHET or WT), we observed an interaction effect for sex and self-grooming environment and an interaction effect for sex and sociability test chamber.LimitationsWhile this study demonstrated a role for forebrain Itgb3 in specific repetitive and social behaviors, it was unable to determine whether forebrain Itgb3 is required for a preference for social novelty, whether cHET are haploinsufficient with respect to repetitive self-grooming and social behaviors, or the nature of the interaction effect for sex and environment/chamber in affected behaviors of cKO.ConclusionsTogether, these findings strengthen the idea that Itgb3 has a specific role in shaping forebrain circuitry that is relevant to endophenotypes of autism spectrum disorder.

μ-Opioid Receptor (Oprm1) Copy Number Influences Nucleus Accumbens Microcircuitry and Reciprocal Social Behaviors.

The μ-opioid receptor regulates reward derived from both drug use and natural experiences, including social interaction, through actions in the nucleus accumbens. Here, we studied nucleus accumbens microcircuitry and social behavior in male and female mice with heterozygous genetic knockout of the μ-opioid receptor (Oprm1+/-). This genetic condition models the partial reduction of μ-opioid receptor signaling reported in several neuropsychiatric disorders. We first analyzed inhibitory synapses in the nucleus accumbens, using methods that differentiate between medium spiny neurons (MSNs) expressing the D1 or D2 dopamine receptor. Inhibitory synaptic transmission was increased in D2-MSNs of male mutants, but not female mutants, while the expression of gephyrin mRNA and the density of inhibitory synaptic puncta at the cell body of D2-MSNs was increased in mutants of both sexes. Some of these changes were more robust in Oprm1+/- mutants than Oprm1-/- mutants, demonstrating that partial reductions of μ-opioid signaling can have large effects. At the behavioral level, social conditioned place preference and reciprocal social interaction were diminished in Oprm1+/- and Oprm1-/- mutants of both sexes. Interaction with Oprm1 mutants also altered the social behavior of wild-type test partners. We corroborated this latter result using a social preference task, in which wild-type mice preferred interactions with another typical mouse over Oprm1 mutants. Surprisingly, Oprm1-/- mice preferred interactions with other Oprm1-/- mutants, although these interactions did not produce a conditioned place preference. Our results support a role for partial dysregulation of μ-opioid signaling in social deficits associated with neuropsychiatric conditions.SIGNIFICANCE STATEMENT Activation of the μ-opioid receptor plays a key role in the expression of normal social behaviors. In this study, we examined brain function and social behavior of female and male mice, with either partial or complete genetic deletion of μ-opioid receptor expression. We observed abnormal social behavior following both genetic manipulations, as well as changes in the structure and function of synaptic input to a specific population of neurons in the nucleus accumbens, which is an important brain region for social behavior. Synaptic changes were most robust when μ-opioid receptor expression was only partially lost, indicating that small reductions in μ-opioid receptor signaling can have a large impact on brain function and behavior.

Bullying among adolescents: The role of skills

Bullying cannot be tolerated as a normal social behavior portraying a child's life. This paper quantifies its negative consequences allowing for the possibility that victims and nonvictims differ in unobservable characteristics. To this end, we introduce a factor analytic model for identifying treatment effects of bullying in which latent cognitive and noncognitive skills determine victimization and multiple outcomes. We use early test scores to identify the distribution of these skills. Individual‐, classroom‐ and district‐level variables are also accounted for. Applying our method to longitudinal data from South Korea, we first show that while noncognitive skills reduce the chances of being bullied during middle school, the probability of being victimized is greater in classrooms with relatively high concentration of boys, previously self‐assessed bullies and students that come from violent families. We report bullying at age 15 has negative effects on physical and mental health outcomes at age 18. We also uncover heterogeneous effects by latent skills, from which we document positive effects on the take‐up of risky behaviors and negative effects on schooling attainment. Our findings suggest that investing in noncognitive development should guide policy efforts intended to deter this problematic behavior. Bullying cognitive and noncognitive skills unobserved heterogeneity C34 C38 I21 J24

Functional MHCI deficiency induces ADHD-like symptoms with increased dopamine D1 receptor expression

Inappropriate synaptic development has been proposed as a potential mechanism of neurodevelopmental disorders, including attention-deficit hyperactivity disorder (ADHD). Major histocompatibility complex class I (MHCI), an immunity-associated molecule expressed by neurons in the brain, regulates synaptic development; however, the involvement of MHCI in these disorders remains elusive. We evaluated whether functional MHCI deficiency induced by β2m−/−Tap1−/− double-knockout in mice leads to abnormalities akin to those seen in neurodevelopmental disorders. We found that functional MHCI deficiency induced locomotor hyperactivity, motor impulsivity, and attention deficits, three major symptoms of ADHD. In contrast, these mice showed normal spatial learning, behavioral flexibility, social behavior, and sensorimotor integration. In the analysis of the dopamine system, upregulation of dopamine D1 receptor (D1R) expression in the nucleus accumbens and a greater locomotor response to D1R agonist SKF 81297 were found in the functional MHCI-deficient mice. Low-dose methylphenidate, used for the treatment of ADHD patients, alleviated the three behavioral symptoms and suppressed c-Fos expression in the D1R-expressing medium spiny neurons of the mice. These findings reveal an unexpected role of MHCI in three major symptoms of ADHD and may provide a novel landmark in the pathogenesis of ADHD

The Electronic Bee Spy: Eavesdropping on Honeybee Communication via Electrostatic Field Recordings.

As a canary in a coalmine warns of dwindling breathable air, the honeybee can indicate the health of an ecosystem. Honeybees are the most important pollinators of fruit-bearing flowers, and share similar ecological niches with many other pollinators; therefore, the health of a honeybee colony can reflect the conditions of a whole ecosystem. The health of a colony may be mirrored in social signals that bees exchange during their sophisticated body movements such as the waggle dance. To observe these changes, we developed an automatic system that records and quantifies social signals under normal beekeeping conditions. Here, we describe the system and report representative cases of normal social behavior in honeybees. Our approach utilizes the fact that honeybee bodies are electrically charged by friction during flight and inside the colony, and thus they emanate characteristic electrostatic fields when they move their bodies. These signals, together with physical measurements inside and outside the colony (temperature, humidity, weight of the hive, and activity at the hive entrance) will allow quantification of normal and detrimental conditions of the whole colony. The information provided instructs how to setup the recording device, how to install it in a normal bee colony, and how to interpret its data.

EDCs Reorganize Brain-Behavior Phenotypic Relationships in Rats.

All species, including humans, are exposed to endocrine-disrupting chemicals (EDCs). Previous experiments have shown behavioral deficits caused by EDCs that have implications for social competence and sexual selection. The neuromolecular mechanisms for these behavioral changes induced by EDCs have not been thoroughly explored. Here, we tested the hypothesis that EDCs administered to rats during a critical period of embryonic brain development would lead to the disruption of normal social preference behavior, and that this involves a network of underlying gene pathways in brain regions that regulate these behaviors. Rats were exposed prenatally to human-relevant concentrations of EDCs (polychlorinated biphenyls [PCBs], vinclozolin [VIN]), or vehicle. In adulthood, a sociosexual preference test was administered. We profiled gene expression of in preoptic area, medial amygdala, and ventromedial nucleus. Prenatal PCBs impaired sociosexual preference in both sexes, and VIN disrupted this behavior in males. Each brain region had unique sets of genes altered in a sex- and EDC-specific manner. The effects of EDCs on individual traits were typically small, but robust; EDC exposure changed the relationships between gene expression and behavior, a pattern we refer to as dis-integration and reconstitution. These findings underscore the effects that developmental exposure to EDCs can have on adult social behavior, highlight sex-specific and individual variation in responses, and provide a foundation for further work on the disruption of genes and behavior after prenatal exposure to EDCs.

A new group housing approach for non-human primate metabolism studies

Understanding the absorption, distribution, metabolism and excretion (ADME) of candidate drugs in preclinical species is an integral part of the safety and efficacy evaluation in drug development. For this purpose, the housing of single animals in metabolism cages has historically been common practice for ADME studies. Whilst mini-pigs and dogs are selected wherever possible, non-human primates (NHPs) are used where there is no suitable scientific alternative. Having undergone only minimal revisions over the past 30 years, the traditional single-housing metabolism cage design for NHPs significantly limits normal vertical movement and social behaviours in primates. Minimising animal suffering and improving welfare is an important aspect of working with animals in research and Novo Nordisk A/S, together with collaborators, has focused on this area for many years. A novel metabolism cage for group housing of NHPs has been designed in a joint collaboration between Novo Nordisk A/S and Covance Inc. The advantages of this novel cage are extensive, including a significantly increased cage volume and ability for socialisation, as well as improvements to alleviate stress and boredom. The excretion balance data from six male NHPs housed in single or group metabolism cages were compared using the radiolabelled test compound [14C]-quetiapine. Welfare, in terms of stress and behaviour, when animals were single or group housed was also assessed. Mean recoveries of radioactivity were shown to be comparable irrespective of housing design (83.2% for group-housed animals vs. 87.1% for single-housed animals), supporting the potential suitability of NHP group housing for future metabolism ADME studies.

Bullying among adolescents: The role of skills

Bullying cannot be tolerated as a normal social behavior portraying a child's life. This paper quantifies its negative consequences allowing for the possibility that victims and nonvictims differ in unobservable characteristics. To this end, we introduce a factor analytic model for identifying treatment effects of bullying in which latent cognitive and noncognitive skills determine victimization and multiple outcomes. We use early test scores to identify the distribution of these skills. Individual‐, classroom‐ and district‐level variables are also accounted for. Applying our method to longitudinal data from South Korea, we first show that while noncognitive skills reduce the chances of being bullied during middle school, the probability of being victimized is greater in classrooms with relatively high concentration of boys, previously self‐assessed bullies and students that come from violent families. We report bullying at age 15 has negative effects on physical and mental health outcomes at age 18. We also uncover heterogeneous effects by latent skills, from which we document positive effects on the take‐up of risky behaviors and negative effects on schooling attainment. Our findings suggest that investing in noncognitive development should guide policy efforts intended to deter this problematic behavior.

Commensal microbe-derived propionic acid mediates juvenile social isolation-induced social deficits and anxiety-like behaviors

Social experiences during early life are thought to be critical for proper social and emotional development. Conversely, social insults during development causes long-lasting behavioral abnormalities later in life. However, how juvenile social deprivation influences social and emotional behaviors remains poorly understood. Here, we show that juvenile social isolation induces a shift in microbial ecology that negatively impacts social and emotional behaviors in adulthood. These behavioral changes, which occur during this critical period are transferable to antibiotic pre-treated mice by fecal microbiota transplant. In addition, juvenile social isolation decreases the expression of oxytocin receptor (OXTR) in the medial prefrontal cortex (mPFC), and increases the amounts of fecal propionic acid (PA), a short-chain fatty acid derived from gut micobiota. Accordingly, infusion with an OXTR antagonist (OXTR-A, l-368,899) specifically in the mPFC or supplementation of PA both can cause social deficits and anxiety-like behaviors in group housed mice. Collectively, our findings reveal that juvenile social experience regulates prefrontal cortical OXTR expression through gut microbiota-produced PA and that is essential for normal social and emotional behaviors, thus providing a cellular and molecular context to understand the consequences of juvenile social deprivation.

MKK7 deficiency in mature neurons impairs parental behavior in mice.

c‐Jun N‐terminal kinases (JNKs) are constitutively activated in mammalian brains and are indispensable for their development and neural functions. MKK7 is an upstream activator of all JNKs. However, whether the common JNK signaling pathway regulates the brain's control of social behavior remains unclear. Here, we show that female mice in which Mkk7 is deleted specifically in mature neurons (Mkk7flox/floxSyn‐Cre mice) give birth to a normal number of pups but fail to raise them due to a defect in pup retrieval. To explore the mechanism underlying this abnormality, we performed comprehensive behavioral tests. Mkk7flox/floxSyn‐Cre mice showed normal locomotor functions and cognitive ability but exhibited depression‐like behavior. cDNA microarray analysis of mutant brain revealed an altered gene expression pattern. Quantitative RT‐PCR analysis demonstrated that mRNA expression levels of genes related to neural signaling pathways and a calcium channel were significantly different from controls. In addition, loss of neural MKK7 had unexpected regulatory effects on gene expression patterns in oligodendrocytes. These findings indicate that MKK7 has an important role in regulating the gene expression patterns responsible for promoting normal social behavior and staving off depression.

Homocysteine Hypothesis on the Impaired Peripheral but Not Central Nervous System Oxytocin Responses in Cystathionine γ-Lyase-Deficient Dam Mice.

An elevated plasma homocysteine level is an independent risk factor for cardiovascular diseases, neurological disorders, and pregnancy complications. We recently demonstrated partial lactation failure in cystathionine γ-lyase-deficient (Cth-/-) dam mice and their defective oxytocin responses in peripheral tissues: uterine (ex vivo) and mammary gland (in vivo). We reasoned that elevated levels of circulatory homocysteine in Cth-/- dam mice counteract with oxytocin-dependent milk ejection from the mammary gland. Based on our observation that those mice displayed normal maternal behaviors against their pups and adult Cth-/- male mice exhibited normal social behaviors against adult wild-type female mice, both of which are regulated by oxytocin in the central nervous system (CNS), we conducted the present study to investigate the amino acid profiles, including total homocysteine, in both blood and cerebrospinal fluid (CSF) of wild-type and Cth-/- female mice before pregnancy and at day 1 of lactation (L1). Serum levels of total homocysteine in wild-type and Cth-/- L1 dam mice were 9.44 and 188 µmol/L, respectively, whereas their CSF levels were below 0.21 (limit of quantification) and 3.62 µmol/L, respectively. Their CSF/serum level ratio was the lowest (1/51.9) among all 20 proteinogenic amino acids, sulfur-containing amino acids, and citrulline/ornithine in Cth-/- mice. Therefore, we hypothesize that the blood-brain barrier protects the CNS from high levels of circulatory homocysteine in Cth-/- dam mice, thereby conferring normal oxytocin-dependent maternal behaviors.

Nanoparticle encapsulated oxytocin increases resistance to induced seizures and restores social behavior in Scn1a-derived epilepsy

Oxytocin (OT) has broad effects in the brain and plays an important role in cognitive, social, and neuroendocrine function. OT has also been identified as potentially therapeutic in neuropsychiatric disorders such as autism and depression, which are often comorbid with epilepsy, raising the possibility that it might confer protection against the behavioral and seizure phenotypes in epilepsy. Dravet syndrome (DS) is an early-life encephalopathy associated with prolonged and recurrent early-life febrile seizures (FSs), treatment-resistant afebrile epilepsy, and cognitive and behavioral deficits. De novo loss-of-function mutations in the voltage-gated sodium channel SCN1A are the main cause of DS, while genetic epilepsy with febrile seizures plus (GEFS+), also characterized by early-life FSs and afebrile epilepsy, is typically caused by inherited mutations that alter the biophysical properties of SCN1A. Despite the wide range of available antiepileptic drugs, many patients with SCN1A mutations do not achieve adequate seizure control or the amelioration of associated behavioral comorbidities. In the current study, we demonstrate that nanoparticle encapsulation of OT conferred robust and sustained protection against induced seizures and restored more normal social behavior in a mouse model of Scn1a-derived epilepsy. These results demonstrate the ability of a nanotechnology formulation to significantly enhance the efficacy of OT. This approach will provide a general strategy to enhance the therapeutic potential of additional neuropeptides in epilepsy and other neurological disorders.

Effects of grazing muzzles on behavior, voluntary exercise, and physiological stress of miniature horses housed in a herd

Grazing muzzles are a popular and effective management tool used to help prevent weight gain in obese-prone equids. Concerns have been raised over their possible negative impact on horse well-being as muzzles may interfere with normal grazing and social behaviors. The objective of this study was to assess the effects of grazing muzzles used for different lengths of time on behavior, voluntary exercise, and physiological stress of grazing horses housed in a herd. Six mature miniature horses (initial BW of 114.9 ± 11.4 kg; BCS of 6.0 ± 0.8) were studied using a 3 × 3 Latin Square repeated measure design with horses receiving one of three treatments daily for a period of 3 weeks. Treatments were unmuzzled (M0), muzzled for 10 h/d (M10, 0830-1830 h), or muzzled for nearly 24 h/d (M24). Horses were housed as a herd on a 0.6 ha grass pasture. Body weight (BW) was assessed weekly. Reaction to muzzle application was scored daily. Behavior was monitored with video twice weekly for two hours a day. An aggressiveness rank was assigned to each horse each period. Physiological stress was assessed weekly using changes in heart rate (HR), indices of heart rate variability, and salivary cortisol concentrations (SC). Voluntary exercise was measured for 24 h twice during each period. Data were analyzed as repeated measures with treatment and wk as main effects. Horses muzzled for 24 h/d lost BW while horses muzzled 0 or 10 h/d gained BW (P = 0.01). Horses muzzled for 24 h/d spent more time grazing (P = 0.04) and less time resting (P = 0.03) than M10 horses. Unmuzzled horses spent more time walking than M24 horses (P < 0.01), more time cantering than M10 (P = 0.02), and more time trotting than M10 and M24 (P = 0.04 and 0.01 respectively). Both muzzled treatments spent less time autogrooming with their mouths than unmuzzled horses (P < 0.01). Horses muzzled for 24 h/d had lower HR than M0 horses (P = 0.01) and higher beat-to-beat intervals than M0 and M10 horses (P = 0.01 and 0.03 respectively) while grazing. There were no effects of treatment on muzzle acceptability score, salivary cortisol, voluntary exercise, or change in aggressiveness rank. In conclusion, muzzling for 24 h/d prevented weight gain and did not cause apparent physiological stress. The lower HR and higher beat-to-beat interval in horses muzzled 24 h may be a potential health benefit and needs further exploration.

Retail Signage During the COVID-19 Pandemic

Early in 2020 the COVID-19 pandemic began to impact countries across the world. Within weeks, people’s normal social behavior had to be changed in order to stop the spread of the disease. In Canada, where this study takes place, governments and public health departments were the primary and trusted information sources. Photographs of retail signs were taken by the author in one neighborhood in a major Canadian city in March and April. Along with descriptive information, the author speculates on the meaning conveyed by the printer-paper signs, beyond their traditional role of supporting wayfinding. Paper’s relative fragility may have simultaneously reflected the uncertainty that people felt in the early days of the pandemic, while its familiar and timeless presence may have provided a sense of emotional security and direction. Marking a return to “business as usual”, stores replaced many, but not all of the informal signs with professionally produced and branded signs suggesting that the early “blind panic” had been replaced by a form of “steady state”. One could say that retailers demonstrated corporate social responsibility through their efforts in creating and posting the signs to create awareness of, educate, and reinforce the new and changing social distancing behaviors.

The autism diagnostic observation schedule: Patterns in individuals with anorexia nervosa.

Studies have used the Autism Diagnostic Observation Schedule (the ADOS-2) in individuals with anorexia nervosa (AN), but the patterns of scores have not been assessed. We examined which subset of the ADOS-2 items best discriminate individuals with AN from healthy controls (HC), and assessed the potential clustering of AN participants based on different profiles of the ADOS-2 item scores. We combined datasets from two previous studies, and (a) compared mean ranks between young AN participants (N = 118) and HC (N = 42), (ii) replicated the item selection procedure of the existing ADOS-2 algorithm to assess sensitivity of items in the AN group, and (c) applied a two-step clustering analysis in the AN group (N = 149). AN participants displayed significantly higher mean ranks than HC participants in five of 32 items. All five items are part of the existing ADOS-2 algorithm. We found two clusters of AN participants; one representing normal social behaviour, comprising 68% of the individuals with AN, and one representing less efficient social behaviour, comprising 32% of individuals with AN. The items comprising the social affective cluster of the existing ADOS-2 algorithm are well suited to assess difficulties with social functioning in individuals with AN.

Social Behavioral Deficits with Loss of Neurofibromin Emerge from Peripheral Chemosensory Neuron Dysfunction

Neurofibromatosis type 1 (NF1) is a neurodevelopmental disorder associated with social and communicative disabilities. The cellular and circuit mechanisms by which loss of neurofibromin 1 (Nf1) results in social deficits are unknown. Here, we identify social behavioral dysregulation with Nf1 loss in Drosophila. These deficits map to primary dysfunction of a group of peripheral sensory neurons. Nf1 regulation of Ras signaling in adult ppk23+ chemosensory cells is required for normal social behaviors in flies. Loss of Nf1 attenuates ppk23+ neuronal activity in response to pheromones, and circuit-specific manipulation of Nf1 expression or neuronal activity in ppk23+ neurons rescues social deficits. This disrupted sensory processing gives rise to persistent changes in behavior beyond the social interaction, indicating a sustained effect of an acute sensory misperception. Together our data identify a specific circuit mechanism through which Nf1 regulates social behaviors and suggest social deficits in NF1 arise from propagation of sensory misinformation.

Excessive β-Catenin in Excitatory Neurons Results in Reduced Social and Increased Repetitive Behaviors and Altered Expression of Multiple Genes Linked to Human Autism.

Multiple human autism risk genes are predicted to converge on the β-catenin (β-cat)/Wnt pathway. However, direct tests to link β-cat up- or down-regulation with autism are largely lacking, and the associated pathophysiological changes are poorly defined. Here we identify excessive β-cat as a risk factor that causes expression changes in several genes relevant to human autism. Our studies utilize mouse lines with β-cat dysregulation in forebrain excitatory neurons, identified as cell types with a convergent expression of autism-linked genes in both human and mouse brains. We show that mice expressing excessive β-cat display behavioral and molecular changes, including decreased social interest, increased repetitive behaviors, reduced parvalbumin and altered expression levels of additional genes identified as potential risk factors for human autism. These behavioral and molecular phenotypes are averted by reducing β-cat in neurons predisposed by gene mutations to express elevated β-cat. Using next-generation sequencing of the prefrontal cortex (PFC), we identify 87 dysregulated genes that are shared between mouse lines with excessive β-cat and autism-like behaviors, but not mouse lines with reduced β-cat and normal social behavior. Our findings provide critical new insights into β-cat, Wnt pathway dysregulation in the brain causing behavioral phenotypes relevant to the disease and the molecular etiology which includes several human autism risk genes.

A novel welfare and scientific approach to conducting dog metabolism studies allowing dogs to be pair housed.

Metabolism cages are designed to conduct absorption, distribution, metabolism and excretion (ADME) studies, enabling an 'excretion balance' scientific objective to be met. Historically, the design of dog metabolism cages has involved single housing. This type of housing has limitations for normal social behaviours and has been largely unchanged for 25-30 years. Improving animal welfare is a focus area for the authorities as well as the industry throughout the European Union. A collaboration was developed between Novo Nordisk and Covance to enhance the design of metabolism cages, allowing dogs to be pair housed. The purpose of the study was to compare excretion balance data from pair-housed and singly housed dogs in order to demonstrate that conducting excretion balance studies with a pair-housing design improves animal welfare without compromising the scientific integrity of the study. A radiolabelled test compound, [14C]-Quetiapine, was selected for this investigation based on its excretion profile. The assessment of the dogs' stress levels was investigated by measuring the levels of serum cortisol as an indicative biomarker. Results were inconclusive due to large variations in cortisol levels. However, dogs appeared calmer in the pair-housing setting. The overall mean recovery (±standard deviation) for pair-housed animals (94.0 ± 0.66% of the dose) was equivalent to that from singly housed dogs (93.0 ± 2.29%). Based on these data, we conclude that pair housing of dogs for future metabolism ADME studies does not compromise the scientific integrity, and therefore is a major progression in the design of these studies, enhancing welfare.

The Influence of Behavioral, Social, and Environmental Factors on Reproducibility and Replicability in Aquatic Animal Models.

The publication of reproducible, replicable, and translatable data in studies utilizing animal models is a scientific, practical, and ethical necessity. This requires careful planning and execution of experiments and accurate reporting of results. Recognition that numerous developmental, environmental, and test-related factors can affect experimental outcomes is essential for a quality study design. Factors commonly considered when designing studies utilizing aquatic animal species include strain, sex, or age of the animal; water quality; temperature; and acoustic and light conditions. However, in the aquatic environment, it is equally important to consider normal species behavior, group dynamics, stocking density, and environmental complexity, including tank design and structural enrichment. Here, we will outline normal species and social behavior of 2 commonly used aquatic species: zebrafish (Danio rerio) and Xenopus (X. laevis and X. tropicalis). We also provide examples as to how these behaviors and the complexity of the tank environment can influence research results and provide general recommendations to assist with improvement of reproducibility and replicability, particularly as it pertains to behavior and environmental complexity, when utilizing these popular aquatic models.

Association of Social Media Use With Social Well-Being, Positive Mental Health, and Self-Rated Health: Disentangling Routine Use From Emotional Connection to Use.

Most studies addressing social media use as a normal social behavior with positive or negative effects on health-related outcomes have conceptualized and measured social media use and its effects in terms of dose-effect relations. These studies focus on measuring frequency and duration of use, and have seldom considered users' emotional connections to social media use and the effects associated with such connections. By using a scale with two dimensions capturing users' integration of social media use into their social routines and their emotional connection to the sites' use, the present study has brought preliminary evidence that may help map where social media use, as a normal social behavior, may be considered beneficial or harmful. Data from a nationally representative sample (n = 1,027) of American adults showed that while routine use is associated with positive health outcomes, emotional connection to social media use is associated with negative health outcomes. These associations have been consistent across three health-related outcomes: social well-being, positive mental health, and self-rated health. The data also showed that the strength of the positive and negative associations of routine use and emotional connection with the health outcomes varies across socioeconomic and racial/ethnic population subgroups. Our findings suggest that the link between social media use and health may not only be captured by and explained in terms of conventional dose-effect approaches but may also require a more sophisticated conceptualization and measurement of the social media use behavior.