Sietse F de Boer

• PhD
• Professor Emeritus at University of Groningen

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. Many animal species show social withdrawal in response to stimuli, including the vinegar fl...

Aggression is a normal and necessary component of social behavior that evolved to promote the protection of self, resources, progeny, and territory. However, excessive aggressiveness and disruptive violent outbursts are common problematic symptoms of multiple psychiatric disorders and represent a significant global burden. Current therapeutic strat...

Although exercise is usually associated with beneficial effects on physical and mental health, patients recovering from surgery may be hampered to perform active exercise. Whole body vibration (WBV) is suggested a passive alternative for physical training. Aim of the present study was to explore the therapeutic potential of WBV compared to physical...

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. I...

Whole body vibration (WBV) is a form of passive exercise by the stimulation of mechanical vibration platform. WBV has been extensively investigated through clinical studies with main focus on the musculoskeletal system. However, pre-clinical data in the context of behavior, memory and motor functions with aged rodents are limited. The aim of this e...

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 f...

Aging is a progressive process leading to functional decline in many domains. Recent studies have shown that physical exercise (PE) has a positive influence on the progression of age-related functional decline, including motor and brain functions. Whole body vibration (WBV) is a form of passive stimulation by mechanical vibration platforms, which o...

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 w...

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...

Inappropriate interpersonal aggression and disruptive violent outbursts are common problematic 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 adapti...

RationaleMany 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...

RationaleSelective 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 b...

Social withdrawal is found across neuropsychiatric disorders and in animal species under various conditions. It has substantial impact on the quality of life in patients suffering from neuropsychiatric disorders. Often it occurs prodromal to the disease, suggesting that it is either an early biomarker or central to its etiology. Healthy social func...

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....

Brain serotonin (5-HT) neurotransmission plays an important role in male sexual behavior and it is well established that activating 5-HT 1A receptors in rats facilitate ejaculatory behavior. However, the relative contribution of 5-HT 1A somatodendritic autoreceptors and heteroreceptors in this pro-sexual behavior is unclear. Moreover, it is unclear...

Aim/Introduction: Excessive aggression is a major source of death and social stress, constituting a significant problem for public health. Understanding the mechanisms underlying the development of aggressive behaviour could help to control it. Interestingly, winning aggressive confrontations results in self-reinforcing pleasurable effects, suggest...

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 t...

The 8th international meeting of the Integrated Brain and Behavior Research Center at the university of Haifa

Brain serotonin (5-HT) plays a key role in aggressive behaviours and related psychopathologies, but its precise mechanism of action remains elusive. Genetic animal models may provide a tool to elucidate the relationship between aggression and serotonin. The present study showed that tryptophan hydroxylase 2 (Tph2) knockout (KO) rats, which exhibit...

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. Furthermor...

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 individua...

Background Currently, neuropsychiatric disorders are separated by convention based clustering of qualitative symptoms, not underlying aetiology. This methodology might be sufficient for general clinical management, but it disregards neurobiology. A better understanding of the neurobiology and the application of this knowledge will lead to enhanced...

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...

The human capacity for uncontrolled aggressiveness and violence inflicts a costly burden on society. Unfortunately, the current intervention strategies and treatment options for curbing these problematic behavioral expressions are largely inadequate. Hence, more fundamental knowledge about the social and neurobiological determinants of aggression i...

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...

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...

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. Yet, whether an aggressive personality trait may predispose individ...

Across the animal kingdom, social interactions, ranging from affiliative cooperative exchanges to intensely aggressive contests, have a fundamental impact upon the health and wellbeing of an individual. Social life is often quite intricate, full of rewards, but also the cause of serious conflict and intense stresses. In this chapter, the sociobiolo...

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...

Understanding the role of the social environment in the development of stress related diseases requires a more fundamental understanding of stress. Stress includes not only the stimulus and the response but also the individual appraisal of the situation. The social environment is not only essential for survival it is at the same time an important s...

Considerable individual differences exist in trait-like patterns of behavioral and physiological responses to salient environmental challenges. This individual variation in stress coping styles has an important functional role in terms of health and fitness. Hence, understanding the neural embedding of coping style variation is fundamental for biob...

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 va...

Background The serotonin (5-HT) deficiency hypothesis of aggression is being seriously challenged by pharmacological data showing robust anti-aggressive effects of 5-HT1A receptor agonists in dose ranges that concomitantly inhibit 5-HT neurotransmission. Hence, an adequate interpretation of the role of 5-HT activity in regulating aggression depends...

Mouse models of aggression have traditionally compared strains, most notably BALB/cJ and C57BL/6. However, these strains were not designed to study aggression despite differences in aggression related traits and distinct reactivity to stress. This study evaluated expression of genes differentially regulated in a stress (behavioral) mouse model of a...

Understanding the etiology of stress-related diseases such as PTSD requires a more fundamental understanding of stress. Since individuals may differ strongly in their response to a stressor, it is argued that stress includes not only the stimulus and the response but also the individual appraisal of the situation. This chapter discusses the stress...

Understanding the etiology of stress-related diseases such as PTSD requires a more fundamental understanding of stress. Since individuals may differ strongly in their response to a stressor, it is argued that stress includes not only the stimulus and the response but also the individual appraisal of the situation. This chapter discusses the stress...

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 rea...

Aggressive behaviour is a major cause of mortality and morbidity. Despite of moderate heritability estimates, progress in identifying the genetic factors underlying aggressive behaviour has been limited. There are currently three genetic mouse models of high and low aggression created using selective breeding. This is the first study to offer a glo...

Aggression is closely related to impulsive behavior both in humans and in animals. To avoid potential negative consequences, aggressive behavior is kept in control by strong inhibitory mechanisms. Failure of these inhibitory mechanisms results in violent behavior. In the present experiments, we investigated whether aggressive behavior is related to...

Oxytocin (OXT) has been implicated in the regulation of social behaviors, including intermale offensive aggression. Recently, we showed that acute enhancement of brain OXT levels markedly suppressed offensive aggression and increased social exploration in resident rats confronted with an intruder in their home territory. Moreover, a different respo...

This video publication explains in detail the experimental protocol of the resident-intruder paradigm in rats. This test is a standardized method to measure offensive aggression and defensive behavior in a semi natural setting. The most important behavioral elements performed by the resident and the intruder are demonstrated in the video and illust...

Personality characteristics, e.g. aggressiveness, have long been associated with an increased risk of cardiac disease. However, the underlying mechanisms remain unclear. In this study we used a rodent model for characterizing cardiac autonomic modulation in rats that differ widely in their level of aggressive behavior. To reach this goal, high-aggr...

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 oxyto...

The first volume in the new Cambridge Handbooks in Behavioral Genetics series, Behavioral Genetics of the Mouse provides baseline information on normal behaviors, essential in both the design of experiments using genetically modified or pharmacologically treated animals and in the interpretation and analyses of the results obtained. The book offers...

Rationale: Preclinical experimental models of pathological aggressive behavior are a sorely understudied and difficult research area. Objectives: How valid, reliable, productive, and informative are the most frequently used animal models of excessive aggressive behavior? Methods: The rationale, key methodological features, supporting data, and...

The current theories of animal personality are based on the observation that individual variation in behavior and physiology appears to be consistent across contexts. Rats of the Roman selection lines have been originally selected for differences in shuttle-box behavior. Besides differences in active avoidance, these animals differ more generally i...

Key points Anxiety disorders reduce both the heart rate variability (HRV) and the sensitivity of the cardiac baroreflex (BRS). This may lead to sudden cardiac death. To elucidate the mechanisms underlying these alterations, male rats were subjected to social defeat sessions that lead to an anxiety‐like state. In this model, HRV and BRS were reduced...

Administration of adenosine-5′-monophosphate (5′-AMP) can induce an artificial but endogenously reversible torpor-like state in mice. The dynamics of body temperature and the relation between body temperature and metabolic rate may indicate the (dis)similarity of this artificial torpor-like state to natural torpor in intact animals. We investigated...

Adverse and stressful experiences during adolescence are often of a social nature. The social defeat model in rats is used as an animal model for bullying in humans. Usually large individual differences in response to social defeat are found. The personality type that is mostly affected and the underlying mechanisms are unknown. We used male rats o...

Cited By (since 1996):4, Export Date: 23 March 2014, Source: Scopus

The mere presence of elevated plasma levels of corticosterone is generally regarded as evidence of compromised well-being. However, environmental stimuli do not necessarily need to be of a noxious or adverse nature to elicit activation of the stress response systems. In the present study, the physiological and neuroendocrine responses to repeated s...

Stressful life events generally enhance the vulnerability for the development of human psychopathologies such as anxiety disorders and depression. The incidence rates of adult mental disorders steeply rises during adolescence in parallel with a structural and functional reorganization of the neural circuitry underlying stress reactivity. However, t...

A coping style (also termed behavioural syndrome or personality) is defined as a correlated set of individual behavioural and physiological characteristics that is consistent over time and across situations. This relatively stable trait is a fundamental and adaptively significant phenomenon in the biology of a broad range of species, i.e. it confer...

Individual variation in behavior and physiology is a widespread and ecologically functional phenomenon in nature in virtually all vertebrate species. Due to domestication of laboratory animals, studies may suffer from a strong selection bias. This paper summarizes behavioral, neuroendocrine and neurobiological studies using the natural individual v...

Violence can be defined as a form of escalated aggressive behavior that is expressed out of context and out of inhibitory control, and apparently has lost its adaptive function in social communication. Little is known about the social and environmental factors as well as the underlying neurobiological mechanisms involved in the shift of normal adap...

Violence was shown to be qualitatively different from functional hyper-aggression in mice selected for high aggression namely Short Attack Latency (SAL), Turku Aggressive (TA) and North Carolina (NC900) strains. This study aimed at investigating whether this adulthood violent phenotype as seen previously in the SAL mice is fixed and hence behaviora...

This study investigated whether trait-like differences in brain monoaminergic functioning relate to differential vulnerability for the long-term neurochemical depletion effects of MDMA. Genetically selected aggressive (SAL) and non-aggressive (LAL) house-mice differing in baseline serotonergic and dopaminergic neurotransmission were administered MD...

Many animal species employ natural hypothermia in seasonal (hibernation) and daily (torpor) strategies to save energy. Facultative daily torpor is a typical response to fluctuations in food availability, but the relationship between environmental quality, foraging behaviour and torpor responses is poorly understood. We studied body temperature resp...

Ecstasy or 3,4-methylenedioxymethamphetamine (MDMA) is a frequently (ab)used recreational drug for its acute euphoric effects but on the long-term may cause neurotoxic damage to serotonin (5-hydroxytryptamine; 5-HT) nerve endings in the brain. Since decreased brain 5-HT function has been strongly associated with several impulse control disorders li...

Reduced brain serotonin (5-HT) activity has been linked to impulsive and violent forms of aggression for decades. Despite a vast accumulation of data pertinent to the above observation, information about the possible mechanisms underlying such a decreased 5-HT functioning is virtually absent. Amongst many, reduced 5-HT biosynthetic capacity is a li...

The present study aims at delineating violence from aggression, using genetically selected high (SAL, TA, NC900) and low (LAL, TNA NC100) aggressive mouse strains. Unlike aggression, violence lacks intrinsic control, environmental constraints as well as functional endpoints. Conventional measures namely latency, frequency and duration were used ini...

Aggressiveness is often considered a life-long, persistent personality trait and is therefore expected to have a consistent neurobiological basis. Recent meta-analyses on physiological correlates of aggression and violence suggest that certain aggression-related psychopathologies are associated with low functioning of the hypothalamo-pituitary-adre...

While individual differences in vulnerability to psychostimulants have been largely attributed to dopaminergic neurotransmission, the role of serotonin is not fully understood. To study the rewarding and motivational properties of cocaine in the serotonin transporter knockout (SERT-/-) rat and the involvement of compensatory changes in 5-HT1A recep...

Recent reviews on the validity of rodent aggression models for human violence have addressed the dimension of pathological, maladaptive, violent forms of aggression in male rodent aggressive behaviour. Among the neurobiological mechanisms proposed for the regulation of aggressive behaviour in its normal and pathological forms, serotonin plays a maj...

Psychopathological violence in criminals and intense aggression in fruit flies and rodents are studied with novel behavioral, neurobiological, and genetic approaches that characterize the escalation from adaptive aggression to violence. One goal is to delineate the type of aggressive behavior and its escalation with greater precision; second, the p...

Impulsivity and aggression have been suggested to inversely correlate with central serotonin (5-HT) levels in a trait-like manner. However, this relationship is far from straightforward. In the present study we addressed the effect of lifelong reduced or absent serotonin transporter (SERT) function, which is associated with constitutively increased...

Differential role of the 5-HT(1A) receptor in aggressive and non-aggressive mice: an across-strain comparison. PHYSIOL BEHAV 00(0) 000-000, 2006. According to the serotonin (5-HT)-deficiency hypothesis of aggression, highly aggressive individuals are characterized by low brain 5-HT neurotransmission. Key regulatory mechanisms acting on the serotone...

Ecological studies on feral populations of mice, fish and birds elucidate the functional significance of phenotypes that differ individually in their behavioral and neuroendocrine response to environmental challenge. Within a species, the capacity to cope with environmental challenges largely determines individual survival in the natural habitat. R...

Despite the growing evidence confirming a negative relationship between violence and sero-tonin neurotransmission in the brain, the development of this relationship is still poorly under-stood. Among the regulatory molecules in the serotonergic neuron, the 5-HT 1A auto-receptor have been proposed as key players in this phenomenon. In this study we...

Ecological studies on feral populations of mice, fish and birds elucidate the functional significance of phenotypes that differ individually in their behavioral and neuroendocrine response to environmental challenge. Within a species, the capacity to cope with environmental challenges largely determines individual survival in the natural habitat. R...

Mice selected for aggressiveness (long and short attack latency mice; LALs and SALs, respectively) constitute a useful tool in studying the neural background of aggressive behavior, especially so as the SAL strain shows violent forms of aggressiveness that appear abnormal in many respects. By using c-Fos staining as a marker of neuronal activation,...

Animal models have contributed considerably to the current understanding of mechanisms underlying the role of stress in health and disease. Despite the progress made already, much more can be made by more carefully exploiting animals' and humans' shared biology, using ecologically relevant models. This allows a fundamental analysis of factors modul...

Animal models have contributed considerably to the current understanding of mechanisms underlying the role of stress in health and disease. Despite the progress made already, much more can be made by more carefully exploiting animals’ and humans’ shared biology, using ecologically relevant models. This allows a fundamental analysis of factors modul...

More than any other brain neurotransmitter system, the indolamine serotonin (5-HT) has been linked to aggression in a wide and diverse range of species, including humans. The nature of this linkage, however, is not simple and it has proven difficult to unravel the precise role of this amine in the predisposition for and execution of aggressive beha...

It is a common belief that male aggressive and sexual behaviour share many of the underlying neurobiological, neurological, pharmacological and neuroendocrine mechanisms. Therefore, we studied brain activation patterns in male rat after performance of aggressive and sexual behaviour and compared serotonergic pharmacology in the same paradigms to de...

Male wild house-mice genetically selected for long attack latency (LAL) and short attack latency (SAL) differ in structural and functional properties of postsynaptic serotonergic-1A (5-HT(1A)) receptors. These mouse lines also show divergent behavioral responses in the forced swimming test (FST, i.e., higher immobility by LAL versus SAL mice). We i...

An important determinant of cardiovascular stress reactivity and morbidity is the individual behavioral strategy of coping with social challenge. This review summarizes the results of a number of studies that we performed in rats, aimed at investigating the relationship between aggression and cardiovascular responsivity under social stress conditio...

In order to study mechanisms involved in the etiology of human affective disorders, there is an abundant use of various animal models. Next to genetic factors that predispose for psychopathologies, environmental stress is playing an important role in the etiology of these mental diseases. Since the majority of stress stimuli in humans that lead to...

This chapter discusses aggressive behavior in rats. Aggressive behavior, although infrequent, is part of life in a colony, particularly during its formation, and these interactions within the group are referred to as dominance or within-group aggressive behavior. As in their feral counterparts, the most potent trigger for aggressive behavior in res...