Activation of serotonergic neurotransmission during the performance of aggressive behavior in rats.

Jeon

Journal of Biological Chemistry

et al. 2009

Voltage-dependent N-type Ca2؉ channels play important roles in the regulation of diverse neuronal functions in the brain, but little is known about its role in social aggressive behaviors. Mice lacking the ␣1B subunit (Ca v 2.2) of N-type Ca 2؉ channels showed markedly enhanced aggressive behaviors to an intruder mouse in the resident-intruder test. The dorsal raphe nucleus (DRN), which contains serotonin neurons, is known to be involved in aggression in animals. We thus examined the DRN neurons in the Ca v 2. (2-6), there was no study of the role of N-type Ca 2ϩ channels in aggression. It is believed that most social animals possess neural mechanisms for the control of aggression, which is essential for maintenance of beneficial relationships among members in a community. Aggression is considered a complex social behavior influenced by both internal (e.g. hormones or genes) and external stimuli (e.g. drive, TV, and frustration etc.) (7). Deficit of the control mechanisms for suppression of aggression might be implicated in the development of violence in various psychiatric disorders, such as attention deficit/hyperactivity disorder (ADHD) and personality disorders (8, 9).The modulation of aggression has been associated with a change in the central serotonin (5-HT) system at the dorsal raphe nucleus (DRN) (10 -14). In the DRN, the 5-HT neuronal activity showing a slow and regular firing pattern (15-17) is known to be influenced by ␥-aminobutyric acid (GABA), 5-HT 1A autoreceptor, and noradrenergic input (17). Furthermore, the modulation of these signals in the DRN affected aggression behaviors in animals (10 -13, 18, 19).It has been shown that the Ca v 2.2 is highly expressed in the DRN of adult rats (20). However, the role of Ca v 2.2 in the DRN has not been examined, nor has the involvement of Ca v 2.2 in the regulation of aggression. Therefore, we have characterized aggression behaviors of Ca v 2.2 Ϫ/Ϫ mice and investigated the properties of the Ca v 2.2 Ϫ/Ϫ DRN neurons. Interestingly, the Ca v 2.2 Ϫ/Ϫ mice exhibited an enhanced aggressive behavior and a reduced inhibitory transmission in the DRN. In addition, Ca v 2.2 Ϫ/Ϫ mice showed an increased level of arginine vasopressin (AVP) in the cerebrospinal fluid (CSF), together with an increase of 5-HT in the hypothalamus. Our results suggest a possibility that the N-type Ca 2ϩ channel plays a critical role in the suppression of aggressive behaviors. EXPERIMENTAL PROCEDURESAnimals-All of the animals were handled in accordance with the animal care and use guidelines of the Korea Institute of * This work was supported by a National Honor Scientist grant from the Ministry of Science and Technology, Korea, and the Chemoinformatics program, the Center-of-Excellence program, and the Top-Brand program in Korea Institute of Science and Technology, Korea. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate t...

Section: Discussionmentioning

confidence: 70%

Deletion of N-type Ca2+ Channel Cav2.2 Results in Hyperaggressive Behaviors in Mice

Jeon

Journal of Biological Chemistry

et al. 2009

“…Secondly, while the changes in the 5-HT system during the aggressive act itself was not addressed in this review, it has to be mentioned that a display of defensive aggressive behavior is positively related to brief spikes of 5-HT neuronal activity. (84) Finally, although these results indicate the important role of the genes encoding pivotal proteins in 5-HT neurotransmission in modulation of aggressive behavior, the 5-HT system is certain to work in concert with other neurotransmitter genes. There is no doubt that a firing 5-HTergic neuron is connected with numerous other cells and receives impulses from different neurotransmitters.…”

Section: Discussionmentioning

confidence: 89%

From genes to aggressive behavior: the role of serotonergic system

2006

Recent investigations in neurogenomics have opened up new lines of research into a crucial genetic problem-the pathway from genes to behavior. This paper concentrates on the involvement of protein elements in the brain neurotransmitter serotonin (5-HT) system in the genetic control of aggressive behavior. Specifically, it describes: (1) the effect of the knockout of MAO A, the principal enzyme in 5-HT degradation, (2) the association of intermale aggression with the polymorphism in the Tph2 gene encoding the key enzyme in 5-HT synthesis in the brain, tryptophan hydroxylase (TPH), and (3) the effect of selective breeding for nonaggressive behavior on 5-HT metabolism, TPH activity and 5-HT(1A) receptors in the brain. The review provides converging lines of evidence that: (1) brain 5-HT contributes to a critical mechanism underlying genetically defined individual differences in aggressiveness, and (2) genes encoding pivotal enzymes in 5-HT metabolism (TPH and MAO A), 5-HT-transporter, 5-HT(1A) and 5-HT(1B) receptors belong to a group of genes that modulate aggressive behavior.

“…Accumulated evidence has suggested an inverse relationship between serotonin level in cerebrospinal fluid (CSF) and brain with impulsivity, or escalated aggression, and suicide (Lee and Coccaro, 2001;van Praag, 1998). In rodents, some studies have shown a similar relationship with decreased serotonin and 5-HIAA levels associated with increased offensive aggression (Chiavegatto et al, 2001;Chiavegatto and Nelson, 2003;Ferrari et al, 2005;van der Vegt et al, 2003).…”

Section: Neurochemical Differencesmentioning

confidence: 95%

Changes in attack behavior and activity in EphA5 knockout mice

et al. 2008

During development, Eph tyrosine kinase receptors and their ephrin ligands function as axon guidance molecules while, in adults, these molecules appear to be involved in the regulation of neural plasticity and emotion. The absence of EphA5 receptor mediated forward signaling may cause alterations in connectivity of neural networks and boundary formation during development, including central monoaminergic systems. In the present studies, we demonstrated altered aggressive responses by animals lacking functional EphA5 receptors. These behavioral changes were accompanied by altered concentrations of serotonin (5-HT) and the metabolite, 5-HIAA, in the hypothalamus. The changes of serotonin activity in hypothalamus also result in increase of body weight in EphA5 knockout mice. Furthermore, EphA5 knockout mice exhibited a significant decrease in activity levels following exposure to naïve intruders in their home cages. We conclude that the EphA5 receptor may be involved in mediation of aggressive behavior regulated, in part, by hypothalamic serotonin.