The human neuropsychiatric risk gene Drd2 is necessary for social functioning across evolutionary distant species.

The Drd2 gene, encoding the dopamine D2 receptor (D2R), was recently indicated as a potential target in the etiology of lowered sociability (i.e., social withdrawal), a symptom of several neuropsychiatric disorders such as Schizophrenia and Major Depression.

Translational validity and methodological underreporting in animal research: A systematic review and meta-analysis of the Fragile X syndrome (Fmr1 KO) rodent model.

Predictive models are essential for advancing knowledge of brain disorders. High variation in study outcomes hampers progress. To address the validity of predictive models, we performed a systematic review and meta-analysis on behavioural phenotypes of the knock-out rodent model for Fragile X syndrome according to the PRISMA reporting guidelines.

Experimentally manipulated food availability affects offspring quality but not quantity in zebra finch meso-populations.

Food availability modulates survival, reproduction and thereby population size. In addition to direct effects, food availability has indirect effects through density of conspecifics and predators. We tested the prediction that food availability in isolation affects reproductive success by experimentally manipulating food availability continuously for 3 years in zebra finches (Taeniopygia guttata) housed in outdoor aviaries.

Repeated victorious and defeat experiences induce similar apical dendritic spine remodeling in CA1 hippocampus of rats.

In this study, apical dendritic spine density of neurons in hippocampal, amygdalar and prefrontal cortical areas was compared in rats that were repeatedly winning or losing social conflicts. Territorial male wild-type Groningen (WTG) rats were allowed multiple daily attacks (>20 times) on intruder males in the resident-intruder paradigm. Frequent winning experiences are known to facilitate uncontrolled aggressive behavior reflected in aggressive attacks on anesthetized males which was also observed in the winners in this study.

Decreased dendritic spine density in posterodorsal medial amygdala neurons of proactive coping rats.

There are large individual differences in the way animals, including humans, behaviorally and physiologically cope with environmental challenges and opportunities. Rodents with either a proactive or reactive coping style not only differ in their capacity to adapt successfully to environmental conditions, but also have a differential susceptibility to develop stress-related (psycho)pathologies when coping fails. In this study, we explored if there are structural neuronal differences in spine density in brain regions important for the regulation of stress coping styles.

Perinatal fluoxetine treatment and dams' early life stress history have opposite effects on aggressive behavior while having little impact on sexual behavior of male rat offspring.

Rationale: Many depressed women continue antidepressant treatment during pregnancy. Selective serotonin reuptake inhibitor (SSRI) treatment during pregnancy increases the risk for abnormal social development of the child, including increased aggressive or defiant behavior, with unknown effects on sexual behavior.

Objectives: Our aim was to investigate the effects of perinatal SSRI treatment and maternal depression, both separately and combined, on aggressive and sexual behavior in male rat offspring.

Perinatal fluoxetine exposure disrupts the circadian response to a phase-shifting challenge in female rats.

Rationale: Selective serotonin reuptake inhibitor (SSRI) antidepressants are increasingly prescribed during pregnancy. Changes in serotonergic signaling during human fetal development have been associated with changes in brain development and with changes in affective behavior in adulthood. The suprachiasmatic nucleus (SCN) is known to be modulated by serotonin and it is therefore assumed that SSRIs may affect circadian rhythms.

Cross-site Reproducibility of Social Deficits in Group-housed BTBR Mice Using Automated Longitudinal Behavioural Monitoring.

Social withdrawal is associated with a variety of neuropsychiatric disorders, including neurodevelopmental disorders. Rodent studies provide the opportunity to study neurobiological mechanisms underlying social withdrawal, however, homologous paradigms to increase translatability of social behaviour between human and animal observation are needed. Standard behavioural rodent assays have limited ethological validity in terms of number of interaction partners, type of behaviour, duration of observation and environmental conditions.

Reproducibility via coordinated standardization: a multi-center study in a Shank2 genetic rat model for Autism Spectrum Disorders.

Inconsistent findings between laboratories are hampering scientific progress and are of increasing public concern. Differences in laboratory environment is a known factor contributing to poor reproducibility of findings between research sites, and well-controlled multisite efforts are an important next step to identify the relevant factors needed to reduce variation in study outcome between laboratories. Through harmonization of apparatus, test protocol, and aligned and non-aligned environmental variables, the present study shows that behavioral pharmacological responses in Shank2 knockout (KO) rats, a model of synaptic dysfunction relevant to autism spectrum disorders, were highly replicable across three research centers.

Subjecting Dams to Early Life Stress and Perinatal Fluoxetine Treatment Differentially Alters Social Behavior in Young and Adult Rat Offspring.

Recently, the putative association between selective serotonin reuptake inhibitor (SSRI) exposure during pregnancy and the development of social disorders in children has gained increased attention. However, clinical studies struggle with the confounding effects of maternal depression typically co-occurring with antidepressant treatment. Furthermore, preclinical studies using an animal model of maternal depression to study effects of perinatal SSRI exposure on offspring social behavior are limited.

Searching for neural and behavioral parameters that predict anti-aggressive effects of chronic SSRI treatment in rats.

Rationale: Only a subset of impulsive aggressive patients benefits from selective serotonin reuptake inhibitor (SSRI) treatment, confirming contradictory results about the association between serotonin (5-hydroxytryptamine, 5-HT) and aggression. This shows the need to define behavioral characteristics within this subgroup to move towards individualized pharmacological treatment of impulsive aggression.

Methods: Here we submitted an outbred strain of Long Evans rats to a crossover design treatment regimen with the SSRI citalopram, to test its anti-aggressive effect.

The Visible Burrow System: A behavioral paradigm to assess sociability and social withdrawal in BTBR and C57BL/6J mice strains.

Disrupted sociability and consequent social withdrawal are (early) symptoms of a wide variety of neuropsychiatric diseases, such as schizophrenia, autism spectrum disorders, depressive disorders and Alzheimer's disease. The paucity of objective measures to translationally assess social withdrawal characteristics has been an important limitation to study this behavioral phenotype, both in human and rodents. The aim of the present study was to investigate sociability and social withdrawal in rodents using an ethologically valid behavioral paradigm, the Visible Burrow System (VBS).

Animal models of excessive aggression: implications for human aggression and violence.

Escalated interpersonal aggression and violence are common symptoms of multiple psychiatric disorders and represent a significant global health issue. Current therapeutic strategies are limited due to a lack of understanding about the neural and molecular mechanisms underlying the 'vicious' shift of normal adaptive aggression into violence, and the environmental triggers that cause it. Development of novel animal models that validly capture the salient features of human violent actions combined with newly emerging technologies for mapping, measuring, and manipulating neuronal activity in the brain significantly advance our understanding of the etiology, neuromolecular mechanisms, and potential therapeutic interventions of excessive aggressive behaviors in humans.

The Serotonin Transporter and Early Life Stress: Translational Perspectives.

The interaction between the serotonin transporter (SERT) linked polymorphic region (5-HTTLPR) and adverse early life stressing (ELS) events is associated with enhanced stress susceptibility and risk to develop mental disorders like major depression, anxiety, and aggressiveness. In particular, human short allele carriers are at increased risk. This 5-HTTLPR polymorphism is absent in the rodent SERT gene, but heterozygous SERT knockout rodents (SERT) show several similarities to the human S-allele carrier, therefore creating an animal model of the human situation.

Trait aggressiveness does not predict social dominance of rats in the Visible Burrow System.

Hierarchical social status greatly influences health and well-being in mammals, including humans. The social rank of an individual is established during competitive encounters with conspecifics. Intuitively, therefore, social dominance and aggressiveness may seem intimately linked.

Transcriptome analysis of genes and gene networks involved in aggressive behavior in mouse and zebrafish.

Despite moderate heritability estimates, the molecular architecture of aggressive behavior remains poorly characterized. This study compared gene expression profiles from a genetic mouse model of aggression with zebrafish, an animal model traditionally used to study aggression. A meta-analytic, cross-species approach was used to identify genomic variants associated with aggressive behavior.