Interactions between anxiety and aggression: role of relevant brain neuropeptides
Final Report Abstract
According to the overall aim of the DFG project on aggression regulation the results contributed to increase our understanding regarding the complex interactions between anxiety, intermale aggression and the involvement of brain neuropeptides such as vasopressin and oxytocin. Comparing rats selectively bred for high (HAB) versus low (LAB) innate anxiety, we could reveal robust differences in aggressive behaviour with low anxiety being associated with high and abnormal forms of aggression in the resident-intruder paradigm, increased neuronal activation within the prelimbic and infralimbic cortices, hypothalamic regions and the Nucleus accumbens, as part of the brain’s reward system. Moreover, high aggression was found to be associated with increased release of dopamine within the Nucleus accumbens and with differential release patterns of vasopressin within the lateral septum and hte bed nucleus of the stria terminalis during the display of low versus high aggression. In an attempt to reveal causes of high and abnormal aggression independent on genetic predisposition, but rather dependent on environmental factors, we could demonstrate that early life stress induced by maternal separation increases juvenile and adult aggressive behaviour in male rats. Specifically, juvenile rats showed more offensive play-fighting and less submissive play probably as a result of long-lasting alterations in vasopressin and a reduction in social memory functions, probably as a result of long-lasting alterations in brain vasopressin activity (increased vasopressin expression in the PVN and the BST, altered vasopressin release patterns and neuropeptide receptor binding). In an attempt to draw detailed conclusions about the association between anxiety and aggression, we found a U-shaped correlation between aggression and anxiety in HAB and LAB rats. Moreover, in HAB, LAB and non-selected rats, selective manipulation of state anxiety by anxiolytic and anxiogenic drugs, respectively, revealed that an anxiolytic drug (diazepam) indeed increased the level of aggression in HA and NAB rats, whereas, in contrast, treatment resulting in increased anxiety reduced the display of various aggression parameters in LAB males during the resident-intruder test in male rats. These data provide information that the level of trait or state anxiety is an important determinant of adult aggression. Further, our attempts to reveal behavioural effects of oxytocin in male rats were only successful in collaboration with the Uhniversity of Groningen using a specific model of high aggression in male wildtype rats. However, in a novel paradigm of female aggression, we could demonstrate that oxytocin reduces the rise in female aggression as a result of repeated aggression training. The novel behavioural aggression paradigm in females as well as the results of oxytocin reducing female aggression formed the basis of a large EU-funded consortium consisting mainly of human researchers in 2013 on female conduct disorders (FemNatCD). In summary, the project was a great success with respect to scientific publications, the promotion of young scientists and subsequent application of further funding.
Publications
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(2010) Aggression and anxiety: social context and neurobiological links. Front Behav Neurosci 4:12-32
Neumann ID, Veenema AH, Beiderbeck DI
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Distinct correlations of vasopressin release within the lateral septum and the bed nucleus of the stria terminalis with the display of intermale aggression. Horm Behav 2010, 58(2):273-281
Veenema AH, Beiderbeck DI, Lukas M, Neumann ID
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Maternal separation enhances offensive play-fighting, basal corticosterone and hypothalamic vasopressin mRNA expression in juvenile male rats. Psychoneuroendocrinology 2010, 34, 463-467
Veenema AH, Neumann ID
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Maternal separation interferes with developmental changes in brain vasopressin and oxytocin receptor binding in male rats. Neuropharmacology 2010, 58(1):78-87
Lukas M, Bredewold R, Neumann ID, Veenema AH
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Vasopressin released within the central amygdala promotes maternal aggression. Eur J Neurosci 2010, 31(5):883-891
Bosch OJ, Neumann ID
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Early life stress impairs social recognition due to a blunted response of vasopressin release within the septum of adult male rats. Psychoneuroendocrinology 2011, 36(6):843-853
Lukas M, Bredewold R, Landgraf R, Neumann ID, Veenema AH
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High and abnormal forms of aggression in rats with extremes in trait anxiety – involvement of the dopamine system in the nucleus accumbens. Psychoneuroendocrinology 2012; 37(12):1969-80
Beiderbeck D, Reber SO, Havasi A, Veenema A, Neumann ID
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Oxytocin mediates rodent social memory within the lateral septum & medial amygdala depending on the relevance of the social stimulus: Male juvenile versus female adult conspecifics. Psychoneuroendocrinology. 2013; 38:916-26
Lukas M, Toth I, Veenema AH, Neumann ID
