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

The research of mechanisms regulating aggressive behavioris one of the main problems of neurogenetics. Tame and highly aggressivestrains of rats (Rattus norvegicus)obtained through long-term selective breeding are a useful modelfor studying the mechanisms of genetically determined defensivebehavior. The neurotransmitter serotonin (5-HT) controls many formsof behavior, including aggression. The activity of the brain 5-HTsystem is regulated not only by its own elements, such as 5-HT1Aand 5-HT7 receptors, but also by various modulators. Among theirvariety, trace amines attract special attention. The main receptorof trace amines, TAAR1, is localized on 5-HT neurons pre- and postsynaptically.NO is also a perspective modulator, it’s synthesis in the brainis activated predominantly by neuronal NO-synthase (NOS1). Here,NOS1 and TAAR1 expression levels in comparison with the level of5-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 aggressiverats was analyzed. In the midbrain and hypothalamus in the aggressiverats compared to tame ones was detected a decrease in the Htr1a mRNA level, while in the frontalcortex there was an increase in the expression level of the Htr7 gene. However, no interstraindifferences in the TAAR1 protein level were detected in the investigatedbrain structures. Moreover, in highly aggressive rats, an increasein the Taar1 mRNA level wasdetected in the midbrain and hippocampus, while in the hypothalamusand frontal cortex Taar1 expressionwas not detected, regardless of the aggressiveness degree. The mostsignificant changes in the 5-HT system of aggressive rats were foundin the frontal cortex; an increase in the 5-HT metabolism indexwas revealed due to an increase in the 5-HIAA level. There was aninverse correlation between the 5-HT metabolism index and NOS1 expression.We hypothesized that the NOS1/NO system is an indicator of the 5-HTsystem functional activity in the genetically determined aggressionconditions.