TY - JOUR

T1 - The Development of Pathological Aggression in Mice during Prolonged Experience of Aggression

T2 - Behavioral and Molecular Changes

AU - Mutovina, A. S.

AU - Sapronova, A. A.

AU - Mezhevalova, P. S.

AU - Airiyants, K. A.

AU - Ryabushkina, Yu A.

AU - Salman, R.

AU - Bondar, N. P.

N1 - Mutovina, A.S., Sapronova, A.A., Mezhevalova, P.S. et al. The Development of Pathological Aggression in Mice during Prolonged Experience of Aggression: Behavioral and Molecular Changes. Neurosci Behav Physi 56, 685–699 (2026). https://doi.org/10.1007/s11055-026-02006-y

PY - 2026/4/29

Y1 - 2026/4/29

N2 - The studies reported here tracked the development of pathological aggression in male CD1 mice during the acquisition of experience of aggression and its possible enhancement after deprivation of aggression. The expression levels of genes in the hypothalamus and nucleus accumbens, which may reflect the development of pathological aggression, were also assessed. Three-month-old outbred male CD1 mice acquired long-term experience of aggression using a “sensory contact” model, where they were exposed to daily confrontations with male C57Bl/6 mice for 30 days. The animals were housed together in the same cage but were separated by a perforated partition, which was removed for only 10 min per day to allow physical contact between the mice. After experience of confrontation, the CD1 mice were housed for another 30 days in the same cages with a permanent C57Bl/6 partner separated by a perforated partition, but this time without physical contact between the animals (the period of deprivation of aggression, olfactory contact only). Aggressive behavior by CD1 males toward C57Bl/6 partners was assessed throughout the experiment (on days 3, 30, and 60), along with manifestations of pathological aggression in a test using introduction of unfamiliar mice: a juvenile conspecific (age one month) or an immobilized adult CD1 male. After the deprivation period, anxiety levels were assessed, along with the plasma corticosterone concentration and gene expression in the hypothalamus (Crh, Crhr1, Crhbp, Nr3c1, Fkbp5, Drd1) and nucleus accumbens (Nr3c1, Fkbp5, Drd1, Drd2, Drd3). Long-term experience of aggression and subsequent deprivation were found to lead to the development of several patterns of aggressive behavior in mice and allowed the animals to be divided into groups: pathological aggressors, non-pathological aggressors, and low-aggression mice. Pathological aggressors demonstrated high levels of abnormal aggression toward immobilized males, along with elevated anxiety after a period of deprivation. Experience of confrontations did not alter corticosterone levels or the expression of genes associated with the glucocorticoid system in the hypothalamus in any of the defined groups of aggressor mice. Changes in the hypothalamic-pituitary-adrenal and dopaminergic systems correlated only in the pathological aggressor group: glucocorticoid receptor gene expression correlated positively with the expression of the dopamine D1 receptor gene in the hypothalamus and nucleus accumbens. These studies also demonstrated that only the dopamine D1 receptor is involved in the development of pathological aggressive behavior and that this occurs in a region-specific manner: its expression was reduced in the hypothalamus and increased in the nucleus accumbens after deprivation of aggression. Thus, long-term experience of aggression leads to the development of a pathological type of behavior and is associated mainly with changes in the dopaminergic system.

AB - The studies reported here tracked the development of pathological aggression in male CD1 mice during the acquisition of experience of aggression and its possible enhancement after deprivation of aggression. The expression levels of genes in the hypothalamus and nucleus accumbens, which may reflect the development of pathological aggression, were also assessed. Three-month-old outbred male CD1 mice acquired long-term experience of aggression using a “sensory contact” model, where they were exposed to daily confrontations with male C57Bl/6 mice for 30 days. The animals were housed together in the same cage but were separated by a perforated partition, which was removed for only 10 min per day to allow physical contact between the mice. After experience of confrontation, the CD1 mice were housed for another 30 days in the same cages with a permanent C57Bl/6 partner separated by a perforated partition, but this time without physical contact between the animals (the period of deprivation of aggression, olfactory contact only). Aggressive behavior by CD1 males toward C57Bl/6 partners was assessed throughout the experiment (on days 3, 30, and 60), along with manifestations of pathological aggression in a test using introduction of unfamiliar mice: a juvenile conspecific (age one month) or an immobilized adult CD1 male. After the deprivation period, anxiety levels were assessed, along with the plasma corticosterone concentration and gene expression in the hypothalamus (Crh, Crhr1, Crhbp, Nr3c1, Fkbp5, Drd1) and nucleus accumbens (Nr3c1, Fkbp5, Drd1, Drd2, Drd3). Long-term experience of aggression and subsequent deprivation were found to lead to the development of several patterns of aggressive behavior in mice and allowed the animals to be divided into groups: pathological aggressors, non-pathological aggressors, and low-aggression mice. Pathological aggressors demonstrated high levels of abnormal aggression toward immobilized males, along with elevated anxiety after a period of deprivation. Experience of confrontations did not alter corticosterone levels or the expression of genes associated with the glucocorticoid system in the hypothalamus in any of the defined groups of aggressor mice. Changes in the hypothalamic-pituitary-adrenal and dopaminergic systems correlated only in the pathological aggressor group: glucocorticoid receptor gene expression correlated positively with the expression of the dopamine D1 receptor gene in the hypothalamus and nucleus accumbens. These studies also demonstrated that only the dopamine D1 receptor is involved in the development of pathological aggressive behavior and that this occurs in a region-specific manner: its expression was reduced in the hypothalamus and increased in the nucleus accumbens after deprivation of aggression. Thus, long-term experience of aggression leads to the development of a pathological type of behavior and is associated mainly with changes in the dopaminergic system.

KW - dopaminergic system

KW - gene expression

KW - hypothalamic-pituitary-adrenal axis

KW - pathological aggression

KW - sensory contact model

KW - патологическая агрессия

KW - гипоталамо-гипофизарно-надпочечниковая ось

KW - дофаминергическая система

KW - модель сенсорного контакта

KW - экспрессия генов

UR - https://www.mendeley.com/catalogue/e78c97a7-701d-35db-9f2c-58803015ddb2/

UR - https://www.scopus.com/pages/publications/105037536439

U2 - 10.1007/s11055-026-02006-y

DO - 10.1007/s11055-026-02006-y

M3 - Article

VL - 56

SP - 685

EP - 699

JO - Neuroscience and Behavioral Physiology

JF - Neuroscience and Behavioral Physiology

SN - 0097-0549

IS - 4

ER -