Objective. In the course of the study, the effect of oxytocin on the behavior and level of monoamines of the brain in aggressive male isolates of the initially low-aggressive C57Bl/6 line with similar indices of highly aggressive white outbred mice was compared. Methods. In experiments on isolated male mice of the low-aggressive C57Bl/6 line and highly aggressive white outbred mice, the effects of oxytocin on the aggressive behavior and the activity of monoaminergic systems of the left and right cerebral hemispheres was investigated. After prolonged social isolation, the male mice, who attacked in the resident-intruder test, were selected for further research. Oxytocin (5 IU/ml, 20μl) was admitrated intranasally. Control animals was treated with saline. With the HPLC-method, in the cerebral cortex, hippocampus, olfactory tubercle and striatum of the left and right sides of the brain the concentrations of dopamine, norepinephrine, serotonin and their metabolites of dioxyphenylacetic, homovaniline and 5-hydroxyindoleacetic acids were measured. Results. Among the male isolates of the C57Bl/6 line, the proportion of aggressive individuals was 56.5%, and among white outbred mice 87.5%. The investigated lines also differed in the attack latency time: aggressive C57Bl/6 mice attacked an average on the 113.1±23.5 second, while in white outbred mice the attack followed on the 35.3±14.7 second (p < 0.01). In the aggressive male isolates of the C57Bl/6 line, which received intranasally saline solution, the content of serotonin and 5-hydroxyindoleacetic acid in the hippocampus was significantly higher on the right. In C57Bl/6, oxytocin reduced the manifestation of aggression caused by prolonged social isolation (p < 0.05), but had no absolute ability to stop this type of behavior. Under its influence, the level of dopamine in the left cortex (p = 0.054), as well as serotonin content in the right hippocampus (p < 0.05) and in the left striatum (p < 0.05) decreased. In addition, the use of oxytocin in C57Bl/6 neutralized the asymmetry of serotonin and 5-hydroxyindoleacetic acid levels in the hippocampus. At the same time there was an asymmetry in the content of dopamine in the cerebral cortex with the predominance of this mediator in the right hemisphere (p < 0.05). In male isolates of highly aggressive white outbred mice, the effect of oxytocin on behavior was not found. However, in these animals oxytocin caused certain changes in monoaminergic systems of the brain. Under the action of oxytocin, the inicial right-sided asymmetry of the level of dopamine metabolites in the striatum and left-sided asymmetry in the level of serotonin in the cortex disappeared. Oxytocin caused an increase in the content of 5-hydroxyacetic acid in the right striatum (p < 0.05) and norepinephrine in the left hippocampus (p < 0.05). In addition, white outbred mice under the influence of oxytocin developed asymmetry with the predominance of norepinephrine in the right olfactory tubercle (p < 0.05). Conclusions. It can be assumed that relatively weak changes in the state of serotonergic and dopaminergic systems against the background of high reactivity of the noradrenergic system are a feature of the reaction of the brain of highly aggressive animals to oxytocin. The data obtained are discussed in terms of the lateralization of neurotransmitter systems responsible for intraspecific aggression caused by prolonged social isolation. (For citation: Karpova IV, Bychkov ER, Marysheva VV, et al. The effect of oxytocin on the level and monoamines turnover in the brain of isolated mice of high- and low-aggressive lines. Reviews on Clinical Pharmacology and Drug Therapy. 2017;15(2):23-30. doi: 10.17816/RCF15223-30).
Involvement of the nitrergic system in the proconvulsant effect of social isolation stress in male mice