The Neurobiological Bases for Development of Pharmacological Treatments of Aggressive Disorders

Abstract

Violence and aggression are major causes of death and injury, thus constituting primary public health problems throughout much of the world costing billions of dollars to society. The present review relates our understanding of the neurobiology of aggression and rage to pharmacological treatment strategies that have been utilized and those which may be applied in the future. Knowledge of the neural mechanisms governing aggression and rage is derived from studies in cat and rodents. The primary brain structures involved in the expression of rage behavior include the hypothalamus and midbrain periaqueductal gray. Limbic structures, which include amygdala, hippocampal formation, septal area, prefrontal cortex and anterior cingulate gyrus serve important modulating functions. Excitatory neurotransmitters that potentiate rage behavior include excitatory amino acids, substance P, catecholamines, cholecystokinin, vasopressin, and serotonin that act through 5-HT2 receptors. Inhibitory neurotransmitters include GABA, enkephalins, and serotonin that act through 5-HT1 receptors. Recent studies have demonstrated that brain cytokines, including IL-1 and IL-2, powerfully modulate rage behavior. IL-1 exerts its actions by acting through 5-HT2 receptors, while IL-2 acts through GABAA or NK1 receptors. Pharmacological treatment strategies utilized for control of violent behavior have met with varying degrees of success. The most common approach has been to apply serotonergic compounds. Others included the application of antipsychotic, GABAergic (anti-epileptic) and dopaminergic drugs. Present and futures studies on the neurobiology of aggression may provide the basis for new and novel treatment strategies for the control of aggression and violence as well as the continuation of existing pharmacological approaches.

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

“…E.g. the lateral hypothalamus showed similar levels of activation in insect hunting rats and their feeding controls, despite the fact that this brain area is considered the most important control region of rat killing in cats and frog and mouse killing in rats [1,4,29]. According to our own observation, muricide and insect hunting are behaviorally different, which may explain these discrepancies.…”

Atypical antipsychotics in the treatment of pathological aggression in children and adolescents: literature review and clinical recommendations

“…4 Neurobiologically, impulsive/affective aggression may be explained as a lack of equilibrium between prefrontal mechanisms of top-down control (orbitofrontal cortex and anterior gyrus cinguli) and the bottom-up limbic stimuli (amygdala and other limbic areas), in which several neurotransmitters, such as serotonin, dopamine, noradrenalin and others, may be involved and may, therefore, be managed pharmacologically. 5,6 Several studies have demonstrated that aggression is a result of the combination of socioenvironmental, psychological and biological factors, and that an environment favorable to personal development may modulate unfavorable genetic characteristics. 7,8 However, biological factors of aggressive behaviors may and should be carefully managed because of probable mid-and long-term impairments and the progression into severe psychiatric disorders in adulthood.…”

Behavioural Neurology of Personality Disorders: A Bi-dimensional Model

“…Defensive rage and panic subsystems could reflect the activation of hypothalamic nuclei in response to alarming stimuli. Such processes clearly involve other vital brain centres such as the amygdala and the brain stem, notably the midbrain's periaqueductal gray matter (PAG) [140][141][142][143].…”