Citation

Takahashi A, Quadros IM, de Almeida RMM, Miczek KA. Curr. Top. Behav. Neurosci. 2012; ePub(ePub): ePub.

Affiliation

Mouse Genomics Resource Laboratory, National Institute of Genetics (NIG), Mishima, Shizuoka, Japan.

Copyright

(Copyright © 2012, Holtzbrinck Springer Nature Publishing Group)

DOI

10.1007/7854_2011_191

PMID

22297576

Abstract

Serotonin (5-HT) has long been considered as a key transmitter in the neurocircuitry controlling aggression. Impaired regulation of each subtype of 5-HT receptor, 5-HT transporter, synthetic and metabolic enzymes has been linked particularly to impulsive aggression. The current summary focuses mostly on recent findings from pharmacological and genetic studies. The pharmacological treatments and genetic manipulations or polymorphisms of a specific target (e.g., 5-HT(1A) receptor) can often result in inconsistent results on aggression, due to "phasic" effects of pharmacological agents versus "trait"-like effects of genetic manipulations. Also, the local administration of a drug using the intracranial microinjection technique has shown that activation of specific subtypes of 5-HT receptors (5-HT(1A) and 5-HT(1B)) in mesocorticolimbic areas can reduce species-typical and other aggressive behaviors, but the same receptors in the medial prefrontal cortex or septal area promote escalated forms of aggression. Thus, there are receptor populations in specific brain regions that preferentially modulate specific types of aggression. Genetic studies have shown important gene-environment interactions; it is likely that the polymorphisms in the genes of 5-HT transporters or rate-limiting synthetic and metabolic enzymes of 5-HT (e.g., MAOA) determine the vulnerability to adverse environmental factors that escalate aggression. We also discuss the interaction between the 5-HT system and other systems. Modulation of 5-HT neurons in the dorsal raphe nucleus by GABA, glutamate and CRF profoundly regulate aggressive behaviors. Also, interactions of the 5-HT system with other neuropeptides (arginine vasopressin, oxytocin, neuropeptide Y, opioid) have emerged as important neurobiological determinants of aggression. Studies of aggression in genetically modified mice identified several molecules that affect the 5-HT system directly (e.g., Tph2, 5-HT(1B), 5-HT transporter, Pet1, MAOA) or indirectly [e.g., BDNF, neuronal nitric oxide (nNOS), αCaMKII, Neuropeptide Y]. The future agenda delineates specific receptor subpopulations for GABA, glutamate and neuropeptides as they modulate the canonical aminergic neurotransmitters in brainstem, limbic and cortical regions with the ultimate outcome of attenuating or escalating aggressive behavior.

Language: en