Enhancement of Aggression Induced by Isolation Rearing is Associated with a Lack of Central Serotonin

• DOI: 10.1007/s12264-019-00373-w
• Publication Date: 2019-04-11T16:04:37Z
• Authors: Yiqiong Liu; Yunong Sun; Xiaoyan Zhao; Ji-Young Kim; Lu Luo; Qian Wang; Xiaolu Meng; Yonghui Li; Nan Sui; Zhou-Feng Chen; Chuxiong Pan; Liang Li; Yan Zhang
• Keywords: Male; 570; Reflex, Startle; Serotonin; STARTLE RESPONSE; Dopamine; 5-HT; 610; Mice, Transgenic; PREPULSE INHIBITION; BRAIN-SEROTONIN; Lmx1b; Mice; 03 medical and health sciences; 0302 clinical medicine; Animals; Maze Learning; IN-VIVO; Mice, Knockout; Social isolation; MEDIAL PREFRONTAL CORTEX; TRYPTOPHAN DEPLETION; Neurosciences; Aggression; Mice, Inbred C57BL; EARLY-LIFE STRESS; Social Isolation; ISOLATION-REARED RATS; WEANING SOCIAL-ISOLATION; Female; Neurosciences & Neurology; BEHAVIOR

Isolation rearing (IR) enhances aggressive behavior, and the central serotonin (5-hydroxytryptamine, 5-HT) system has been linked to IR-induced aggression. However, whether the alteration of central serotonin is the cause or consequence of enhanced aggression is still unknown. In the present study, using mice deficient in central serotonin Tph2-/- and Lmx1b-/-, we examined the association between central serotonin and aggression with or without social isolation. We demonstrated that central serotonergic neurons are critical for the enhanced aggression after IR. 5-HT depletion in wild-type mice increased aggression. On the other hand, application of 5-HT in Lmx1b-/- mice inhibited the enhancement of aggression under social isolation conditions. Dopamine was downregulated in Lmx1b-/- mice. Similar to 5-HT, L-DOPA decreased aggression in Lmx1b-/- mice. Our results link the serotoninergic system directly to aggression and this may have clinical implications for aggression-related human conditions.