Social and neural determinants of aggressive behavior: pharmacotherapeutic targets at serotonin,dopamine and gamma-aminobutyric acid systems |
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Authors: | Miczek Klaus A Fish Eric W De Bold Joseph F De Almeida Rosa M M |
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Institution: | (1) Department of Psychology, Tufts University, 530 Boston Ave. (Bacon Hall), Medford, MA 02155, USA,;(2) Department of Psychiatry, Tufts University, Boston, Massachusetts, USA,;(3) Department of Pharmacology, Tufts University, Boston, Massachusetts, USA,;(4) Department of Neuroscience, Tufts University, Boston, Massachusetts, USA,;(5) Current address: UNISINOS, Centro 2, Nucleo de Neurociencias, Sao Leopoldo, Brazil, |
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Abstract: | Abstract
Background and rationale. Aggressive outbursts that result in harm and injury present a major problem for the public health and criminal justice systems,
but there are no adequate treatment options. Obstacles at the level of social policy, institutional regulation, and scientific
strategy in developing animal models continue to impede the development of specific anti-aggressive agents for emergency and
long-term treatments.
Objective. To be more relevant to the clinical situation, preclinical aggression research has begun to focus on the neurobiological
determinants of escalated aggressive behavior that exceeds species-typical patterns. It is the goal of this review to examine
novel pharmacological and molecular tools that target the neural mechanisms for different kinds of aggressive behavior more
selectively than previously possible and to outline potential pharmacotherapeutic options.
Results and conclusions. (1) The preclinical focus on the behavioral characteristics and determinants of intense aggression promises to be most relevant
to the clinical distinction between the proposed impulsive-reactive-hostile-affective subtypes of human aggression and the
controlled-proactive-instrumental-predatory subtypes of aggression. The neural circuits for many types of human and animal
aggression critically involve serotonin, dopamine and γ-aminobutyric acid (GABA) and specific receptor subtypes. (2) The dynamic
changes in frontal cortical serotonin that are triggered by engaging in aggressive behavior imply that serotonergic drug effects
are largely determined by the functional state of the receptors at the time of drug treatment. Of the numerous 5-HT receptors
currently identified, the 5-HT1B receptors offer a promising target for reducing impulsive aggressive behavior, particularly if the action can be limited
to sites in the central nervous system. (3) Aggressive confrontations are salient stressors, both for the aggressor as well
as the victim of aggression, that are accompanied by activation of the mesocorticolimbic but not the striatal dopamine system.
Dopaminergic manipulations, particularly targeting the D2 receptor family, can influence aggressive behavior in animals and human patients, suggesting that mesocorticolimbic dopamine
may have important enabling or permissive functions. (4) GABA is critical in the neurochemical control of aggressive behavior
as evidenced by studies that directly modify GABAergic neurotransmission and neurochemical studies that correlate GABA measurements
with aggressive behavioral responses in several animal species. The GABAA receptor complex is a mechanism through which certain benzodiazepines and alcohol enhance and inhibit aggressive behaviors.
Social and pharmacological experiences decisively determine the effects of GABAergic positive modulators on aggression.
Electronic Publication |
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Keywords: | Aggression Serotonin Dopamine GABA Benzodiazepines SSRI 5-HT receptor GABAA receptor Alcohol |
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