Preclinical models of conduct disorder – principles and pharmacologic perspectives

Haller, József

doi:10.1016/j.neubiorev.2016.05.032

Cited by 17 publications

(8 citation statements)

References 92 publications

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“…Instrumental (proactive) aggression appears associated with blunted, whereas emotional (reactive) aggression seems to be associated with upregulated HPA-axis function (McBurnett et al, 2003 , 2005 ; Kempes et al, 2005 ; van Bokhoven et al, 2005 ; Lopez-Duran et al, 2009 ; O'Neal et al, 2010 ; Poustka et al, 2010 ; van Honk et al, 2010 ; Geniole et al, 2011 ; Stoppelbein et al, 2014 ). Noteworthy, a similar dichotomy was found in animal models (Haller, 2016 ).…”

Section: Glucocorticoid Deficits and Aggression In Humanssupporting

confidence: 63%

The Role of the Lateral Hypothalamus in Violent Intraspecific Aggression—The Glucocorticoid Deficit Hypothesis

Haller

2018

Front. Syst. Neurosci.

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This review argues for a central role of the lateral hypothalamus in those deviant forms of aggression, which result from chronic glucocorticoid deficiency. Currently, this nucleus is considered a key region of the mechanisms that control predatory aggression. However, recent findings demonstrate that it is strongly activated by aggression in subjects with a chronically downregulated hypothalamus-pituitary-adrenocortical (HPA) axis; moreover, this activation is causally involved in the emergence of violent aggression. The review has two parts. In the first part, we review human findings demonstrating that under certain conditions, strong stressors downregulate the HPA-axis on the long run, and that the resulting glucocorticoid deficiency is associated with violent aggression including aggressive delinquency and aggression-related psychopathologies. The second part addresses neural mechanisms in animals. We show that the experimental downregulation of HPA-axis function elicits violent aggression in rodents, and the activation of the brain circuitry that originally subserves predatory aggression accompanies this change. The lateral hypothalamus is not only an integral part of this circuitry, but can elicit deviant and violent forms of aggression. Finally, we formulate a hypothesis on the pathway that connects unfavorable social conditions to violent aggression via the neural circuitry that includes the lateral hypothalamus.

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Section: Glucocorticoid Deficits and Aggression In Humanssupporting

confidence: 63%

The Role of the Lateral Hypothalamus in Violent Intraspecific Aggression—The Glucocorticoid Deficit Hypothesis

Haller

2018

Front. Syst. Neurosci.

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“…However, aggression may also be expressed out of context or excessively. In humans, such abnormal aggressive behavior is listed as a core symptom of several psychiatric disorders, such as conduct disorder, anti-social personality disorder, schizophrenia, bipolar disorder, and post-traumatic stress disorder ( Nelson and Chiavegatto, 2001 ; Glenn et al, 2013 ; Reidy et al, 2015 ; Haller, 2016 ). The fact that aggression often becomes pathological ( Glenn et al, 2013 ; Reidy et al, 2013 , 2015 ), associated with its potential to cause a burden to society ( Sourander et al, 2007 ; Reidy et al, 2015 ; Sumner et al, 2015 ), has driven scientists to use model organisms such as songbirds, rodents, cats and primates to study the neurobiology of aggressive behavior ( Lischinsky and Lin, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Synthetic Oxytocin and Vasopressin Act Within the Central Amygdala to Exacerbate Aggression in Female Wistar Rats

2022

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Exacerbated aggression is a high-impact, but poorly understood core symptom of several psychiatric disorders, which can also affect women. Animal models have successfully been employed to unravel the neurobiology of aggression. However, despite increasing evidence for sex-specificity, little is known about aggression in females. Here, we studied the role of the oxytocin (OXT) and arginine vasopressin (AVP) systems within the central amygdala (CeA) on aggressive behavior displayed by virgin female Wistar rats using immunohistochemistry, receptor autoradiography, and neuropharmacology. Our data show that CeA GABAergic neurons are activated after an aggressive encounter in the female intruder test. Additionally, neuronal activity (pERK) negatively correlated with the display of aggression in low-aggressive group-housed females. Binding of OXT receptors, but not AVP-V1a receptors, was increased in the CeA of high-aggressive isolated and trained (IST) females. Finally, local infusion of either synthetic OXT or AVP enhanced aggression in IST females, whereas blockade of either of these receptors did not affect aggressive behavior. Altogether, our data support a moderate role of the CeA in female aggression. Regarding neuropeptide signaling, our findings suggest that synthetic, but not endogenous OXT and AVP modulate aggressive behavior in female Wistar rats.

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“…For example, prenatal alcohol is a common triggering factors for clinical CD (Easey, Dyer, Timpson, & Munafò, 2019), in zebrafish impairing social behaviors as adults (Fernandes & Gerlai, 2009; Fernandes, Rampersad, & Gerlai, 2015). Various animal models have also been used to study the role of environmental modulation in CNS disorders and their therapies (De Abreu, et al., 2019; Haller, 2018; Hernandez‐Lallement, van Wingerden, & Kalenscher, 2018; Homberg et al., 2016; Laviola et al., 2017; Meyer, Feldon, & Fatemi, 2009). For instance, maternal separation increases social conflict in rodents (Veenema & Neumann, 2009), whereas early exposure to various drugs increases aggression and impairs learning in rodents (Meek, Myren, Sturm, & Burau, 2007; Miczek & de Almeida, 2001), typical signs of CD.…”

Section: Discussionmentioning

confidence: 99%

Zebrafish models of impulsivity and impulse control disorders

Abreu

Giacomini

Genário

et al. 2020

Eur J of Neuroscience

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Impulse control disorders (ICDs) are characterized by generalized difficulty controlling emotions and behaviors. ICDs are a broad group of the central nervous system (CNS) disorders including conduct disorder, intermittent explosive, oppositional‐defiant disorder, antisocial personality disorder, kleptomania, pyromania and other illnesses. Although they all share a common feature (aberrant impulsivity), their pathobiology is complex and poorly understood. There are also currently no ICD‐specific therapies to treat these illnesses. Animal models are a valuable tool for studying ICD pathobiology and potential therapies. The zebrafish (Danio rerio) has become a useful model organism to study CNS disorders due to high genetic and physiological homology to mammals, and sensitivity to various pharmacological and genetic manipulations. Here, we summarize experimental models of impulsivity and ICD in zebrafish and highlight their growing translational significance. We also emphasize the need for further development of zebrafish ICD models to improve our understanding of their pathogenesis and to search for novel therapeutic treatments.

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Preclinical models of conduct disorder – principles and pharmacologic perspectives

Cited by 17 publications

References 92 publications

The Role of the Lateral Hypothalamus in Violent Intraspecific Aggression—The Glucocorticoid Deficit Hypothesis

The Role of the Lateral Hypothalamus in Violent Intraspecific Aggression—The Glucocorticoid Deficit Hypothesis

Synthetic Oxytocin and Vasopressin Act Within the Central Amygdala to Exacerbate Aggression in Female Wistar Rats

Zebrafish models of impulsivity and impulse control disorders

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