The Psychopharmacology of Aggressive Behavior

Abstract

Patients with mental disorders are at an elevated risk for developing aggressive behavior. In the last 19 years, the psychopharmacological treatment of aggression has changed dramatically because of the introduction of atypical antipsychotics into the market and the increased use of anticonvulsants and lithium in the treatment of aggressive patients.Using a translational medicine approach, this review (part 1 of 2) examines the neurobiology of aggression, discussing the major neurotransmitter systems implicated in its pathogenesis, namely, serotonin, glutamate, norepinephrine, dopamine, and γ-aminobutyric acid, and also their respective receptors. The preclinical and clinical pharmacological studies concerning the role of these neurotransmitters have been reviewed, as well as research using transgenic animal models. The complex interaction among these neurotransmitters occurs at the level of brain areas and neural circuits such as the orbitoprefrontal cortex, anterior cortex, amygdala, hippocampus, periaqueductal gray, and septal nuclei, where the receptors of these neurotransmitters are expressed. The neurobiological mechanism of aggression is important to understand the rationale for using atypical antipsychotics, anticonvulsants, and lithium in treating aggressive behavior. Further research is necessary to establish how these neurotransmitter systems interact with brain circuits to control aggressive behavior at the intracellular level.

Cerebrospinal fluid glutamate concentration correlates with impulsive aggression in human subjects

“…These data are consistent with the preclinical literature in suggesting a facilitating role for glutamate in aggressive behavior (Comai et al, 2012). A synthesis of this work posits that glutamate can stimulate NMDA, AMPA, and metabotropic receptors in the amygdala, medial hypothalamus, and periaqueductal gray to enhance defensive-rage behavior.…”

Rapamycin attenuates aggressive behavior in a rat model of pilocarpine-induced epilepsy

“…To further understanding the mechanism of action of rapamycin, one possible approach would be to use either anti-epileptic or anti-psychiatric drugs as probes to selectively target each of them individually. However, there is an overt limitation in this method because many standard anti-epileptic drugs such as valproic acid and phenytoin not only suppress seizures, but also possess anti-psychiatric effect (Comai et al, 2012a, Comai et al, 2012b). Similarly, psychiatric drugs were also reported to have various effects on epilepsy (Ruffmann et al, 2006).…”

The role of monoamine oxidase A in aggression: Current translational developments and future challenges

“…Accordingly, studies in rodents have shown that the accumbal concentrations of this neurotransmitter are increased before, during and after an aggressive encounter (de Almeida et al, 2005). Clinical evidence has also shown the implication of hyperactive dopaminergic limbic transmission in reactive aggression (Comai et al, 2012). Furthermore, given the importance of accumbal dopamine signaling in habit formation, it is likely that this substrate may play a role in the formation of aggressive habits and the perpetuation of antisocial behaviors.…”