Neural background of glucocorticoid dysfunction‐induced abnormal aggression in rats: involvement of fear‐ and stress‐related structures

Abstract

Glucocorticoid hypofunction is associated with persistent aggression in some psychologically disordered human subjects and, as reported recently, induces abnormal forms of aggression in rats. Here we report on the effects of glucocorticoid hypofunction on aggression-induced neural activation. Rats were adrenalectomized, and implanted with low-release glucocorticoid pellets. After one week recovery, they were challenged by an unfamiliar intruder in their home-cage. Neural activation was studied by c-Fos protein immunocytochemistry. Aggressive encounters in controls induced c-Fos activation in all brain areas relevant for the control of aggression (cortex, amygdala, septum, hypothalamus, periaqueductal grey and the locus coeruleus). Very intense c-Fos activation was observed in the medial amygdala, the hypothalamic attack area and the periaqueductal grey matter which constitute a downward stimulatory stream that activates attack behaviour. The experimentally induced glucocorticoid hypofunction dramatically increased attacks targeted towards vulnerable parts of the opponent's body (mainly the head). This abnormal behaviour was not associated with changes in the activation of brain centres involved in the control of aggression. However, the activation of brain centres involved in both the stress response (the parvocellular part of the hypothalamic paraventricular nucleus) and fear reactions (central amygdala) were markedly increased. An acute glucocorticoid treatment abolished both behavioural and neural consequences of glucocorticoid hypofunction. Our data suggest that glucocorticoid hypofunction-induced abnormal forms of aggressiveness are related to increased sensitivity to stressors and fear-eliciting stimuli. This assumption is supported by the finding that fearful situations induce attack patterns in intact rats that are similar to those induced by glucocorticoid hypofunction.

Neural mechanisms of predatory aggression in rats—Implications for abnormal intraspecific aggression

“…Highy similar findings were obtained in the cockroach-hunting model of predatory aggression [28]. The over-activation of the central nucleus is also well-documented in the glucocorticoid-dysfunction model, where predatorylike attacks are shown in a social context [19,21,47]. No medial amygdala activation surpassing that seen in controls were observed in the rat models discussed here except for muricide.…”

“…We found that in this model, aggressive encounters increase the activation of the lateral hypothalamus, central amygdala and ventral periaqueductal grey (PAG) above the levels seen in controls submitted to fights (i.e. these regions were overactivated) [4,18,19,21,22]. Moreover, the activation of the central amygdala and lateral hypothalamus correlated significantly with the share of abnormal, predatory-like attacks in this model [22].…”

“…It was also used to study the brain mechanisms of cockroach hunting, another model of rat predatory aggression [27,28]. The study presented here was performed to serve as a comparison for other models of predatory aggression (stimulation-induced aggression in cats [1,4], and cockroach hunting in rats [27,28]), as well as for certain models of abnormal aggression in rats (glucocorticoid dysfunction model, [18,21,35]). These models will be compared by starting with the hypothalamus that plays crucial roles in the elicitation of biting attacks in both cats and rats [1].…”

“…Interestingly, the lateral hypothalamus was also overactivated in the glucocorticoid dysfunction model of abnormal aggression, the subjects of which deliver bites to highly vulnerable targets of their opponents (head, throat and belly) on the background of diminished social signaling of attacks by threats, which make their behavior similar to that seen during predation [22]. In contrast to the lateral hypothalamic region, the mediobasal hypothalamus (often called the 'hypothalamic attack area' in rats) elicits affective aggression in both cats and rats, and is activated by resident/intruder interactions in the latter species [1,4,21,37,39,40]. Cat studies revealed a reciprocal inhibition between the lateral and mediobasal regions, which involves a context-dependent control of attacks, making social and predatory aggressions mutually exclusive [4,39].…”

Intermale aggression in corticotropin-releasing factor receptor 1 deficient mice

“…Thus, lower attacks to the ventral portion of the mid-section (including belly) of the intruder by KO mice would be consistent with lower glucorticoid activity in these mice. However, decreased [16] or increased [2,17] levels of glucocorticoids can heightened intermale aggression in rats and mice, so it is not clear how altering glucocorticoids in the KO mice would affect aggressive output. Glucocorticoid replacement was unable to rescue anxiety measure differences between genotypes [35], so altering steroids in these mice may have little or no impact on aggression as well.…”