Maternal separation early in life induces excessive activity of the central amygdala related to abnormal aggression

• Published in: Journal of neurochemistry 2023-12, Vol.167 (6), p.778-794
• Main Authors: Ohta, Ken‐ichi, Araki, Chihiro, Ujihara, Hidetoshi, Iseki, Keizo, Suzuki, Shingo, Otabi, Hikari, Kumei, Haruki, Warita, Katsuhiko, Kusaka, Takashi, Miki, Takanori
• Format: Article
• Language: English
• Subjects: adverse environment; Aggression; Aggression - physiology; Aggressive behavior; Aggressiveness; Amygdala; Animals; central amygdala; Central Amygdaloid Nucleus; Child abuse & neglect; Delinquency; Epidemiology; Genetics; Humans; Information processing; Male; Maternal Deprivation; maternal separation; Offspring; Optics; optogenetics; Predatory behavior; Prey; Rats; Rats, Sprague-Dawley; Risk factors; Separation; Violence
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/jnc.16020

Epidemiological studies have indicated that child maltreatment, such as neglect, is a risk factor of escalated aggression, potentially leading to delinquency and violent crime in the future. However, little is known about the mechanisms by which an early adverse environment may later cause violent behavior. In this study, we aimed to thoroughly examine the association between aggression against conspecific animals and the activity of amygdala subnuclei using the maternal separation (MS) model, which is a common model of early life stress. In the MS group, pups of Sprague–Dawley rats were separated from their dam during postnatal days 2–20 (twice a day, 3 h each). We only included 9‐week‐old male offspring for each analysis and compared the MS group with the mother‐reared control group; both groups were raised by the same dam during postnatal days 2–20. The results revealed that the MS group exhibited higher aggression and excessive activity of only the central amygdala (CeA) among the amygdala subnuclei during the aggressive behavior test. Moreover, a significant positive correlation was observed between higher aggression and CeA activation. While CeA activity is known to be involved in hunting behavior for prey, some previous studies have also indicated a relationship between CeA and intraspecific aggression. It remains unclear, however, whether excessive CeA activity directly induces intraspecific aggression. Therefore, we stimulated the CeA using optogenetics with 8‐week‐old rats to clarify the relationship between intraspecific aggression and CeA activity. Notably, CeA activation resulted in higher aggression, even when the opponent was a conspecific animal. In particular, bilateral CeA activation resulted in more severe displays of aggressive behavior than necessary, such as biting a surrendered opponent. These findings suggest that an adverse environment during early development intensifies aggression through excessive CeA activation, which can increase the risk of escalating to violent behavior in the future. The present study was conducted using the maternal separation (MS) model to clarify the relationship between an early adverse environment and aggression. MS during early development increased aggression after maturation, which was strongly correlated with excessive activation in the central amygdala (CeA) rather than in the lateral/basolateral and medial amygdala. In addition, an optogenetic experiment revealed that CeA activation induced exces