Modulators of the Brain Serotonin System in Rats with Genetically Determined Aggression towards Man or Its Absence

The research of mechanisms regulating aggressive behavior is one of the main problems of neurogenetics. Tame and highly aggressive strains of rats (Rattus norvegicus) obtained through long-term selective breeding are a useful model for studying the mechanisms of genetically determined defensive behavior. The neurotransmitter serotonin (5-HT) controls many forms of behavior, including aggression. The activity of the brain 5-HT system is regulated not only by its own elements, such as 5-HT1A and 5-HT7 receptors, but also by various modulators. Among their variety, trace amines attract special attention. The main receptor of trace amines, TAAR1, is localized on 5-HT neurons pre- and postsynaptically. NO is also a perspective modulator, it’s synthesis in the brain is activated predominantly by neuronal NO-synthase (NOS1). Here, NOS1 and TAAR1 expression levels in comparison with the level of 5-HT, its main metabolite (5-HIAA) and mRNA of 5-HT receptors (Htr1a, Htr7), as well as the expression and activity of TPH2 in the midbrain, hippocampus, hypothalamus and frontal cortex of tame and aggressive rats was analyzed. In the midbrain and hypothalamus in the aggressive rats compared to tame ones was detected a decrease in the Htr1a mRNA level, while in the frontal cortex there was an increase in the expression level of the Htr7 gene. However, no interstrain differences in the TAAR1 protein level were detected in the investigated brain structures. Moreover, in highly aggressive rats, an increase in the Taar1 mRNA level was detected in the midbrain and hippocampus, while in the hypothalamus and frontal cortex Taar1 expression was not detected, regardless of the aggressiveness degree. The most significant changes in the 5-HT system of aggressive rats were found in the frontal cortex; an increase in the 5-HT metabolism index was revealed due to an increase in the 5-HIAA level. There was an inverse correlation between the 5-HT metabolism index and NOS1 expression. We hypothesized that the NOS1/NO system is an indicator of the 5-HT system functional activity in the genetically determined aggression conditions.