The role of serotonin in the modulation of aggression

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The full article with all sources can be found on the main page: https://antiviolence.io/en/#5_ht_agonists_experiments

It is worth starting from the evidence that can confirm the existence of the violence inhibitor as a specific neurophysiological mechanism. Also, it can confirm the validity of the conclusion regarding defensive aggression as a functional and evolutionarily optimal form of behavior, which is not contradicted by the function of the violence inhibitor.

A study on how serotonin shapes moral judgments and behavior suggests that a mechanism similar to Blair's VIM operates for imagined harms in the case of moral judgments. The neurotransmitter serotonin (5-HT) is responsible for the functioning of this mechanism, and the model developed in the study explains its parallel role in the inhibition of actual harm (in the case of aggression) and imagined harm (in the case of moral judgments). Many other studies also confirm the key role of serotonin in the modulation of aggression in animals and humans.

Various experiments conducted on rats and mice showed that some agonists of the 5-HT_1A and 5-HT_1B receptors (these chemical compounds cause a biological response in receptors or, put simply, activate them) are able to suppress offensive aggression while not affecting defensive aggression as well as other forms of behavior.

For example, in various experiments with mice and rats like the resident-intruder paradigm, when administered into the lateral ventricles of the brain, agonists such as TFMPP and eltoprazine had a significant effect in reducing aggressiveness while not affecting defensive behavior. This effect was associated with the activation of postsynaptic 5-HT_1B receptors. It should be noted that the administration of eltoprazine into another part of the brain, the dorsal raphe nucleus, had a nonselective effect, suppressing both types of aggression and other forms of social communication, making the animals behave passively. Administration of a selective 5-HT_1A agonist called F15599 into the ventro-orbital prefrontal cortex of male mice reduced the manifestation of intense elements of aggression, biting during attacks, as well as lateral threat postures (demonstrating aggressive intentions), without affecting non-intense manifestations of aggression and other forms of behavior.

Administration of the 5-HT_1B agonist CP-94253 into the ventro-orbital prefrontal cortex of mice also reduced the frequency of attack bites and the manifestation of lateral threat postures. The importance of 5-HT_1B receptors in the inhibition of aggression was also demonstrated in an experiment where administration of the agonist anpirtoline reduced the manifestation of various forms of aggression in mice, including aggression from social interaction with an opponent and aggression from frustration. An extremely selective effect compared to other agonists showed administration of the 5-HT_1A agonist alnespirone to rats. Again, this did not affect the defensive behavior in the case when the individual encountered an aggressive conspecific, as well as other forms of behavior.

The serotonergic (5-HT) system, and more specifically the 5-HT_1A and 5-HT_1B receptors, plays a key role in the modulation of aggression in various species, including humans. It should be noted that in the case of 5-HT_1A receptors, the activation of postsynaptic receptors in the amygdala, frontal cortex, and hypothalamus leads to the inhibition of aggression, while the activation of presynaptic receptors inhibits the functioning of the 5-HT system itself, which, on the contrary, can lead to aggressive behavior.