Brain monoamines in early ontogenesis and selection effects in rats with behavioral stereotypy

The rat strain with hereditary stereotypy in the form of pendulum movements (PM) can be considered as a new model of audiogenic epilepsy. The purpose of this study was to investigate levels of brain monoamines (MA) at the early stages of postnatal ontogenesis in PM rats, as well as to assess the severity of PM, audiogenic epilepsy and aggressiveness in adult PM rats of different generations of selection. The effects of selection in adult rats with PM in 52–54 generations of selection included an increase in the amplitude of PM, an increase in the frequency and intensity of clonic-tonic seizures, an increase in the duration of postictal catalepsy and increased aggressiveness. The higher level of serotonin (5HT) in the brainstem was shown in PM pups compared to Wistar pups at the age of 14 days. The higher level of the serotonin metabolite, 5-hydroxyindoleacetic acid (5HIAA), was found in the cortex of 14-day-old PM pups. Higher levels of dopamine metabolites DOPAC and homovanillic acid (HVA) were found in the cortex of 14-day-old PM rat pups. But the level of HVA in the cortex was lower in 10-day-old PM pups than it in Wistar pups. Higher levels of dopamine (DA) and its metabolite dihydroxyphenylacetic acid (DOPAC) were shown in the brainstem of PM pups compared to Wistar pups at the specified age. The reduced dopamine turnover was shown in the brainstem of 14-day-old PM pups in compare with Wistar pups. This data indicate changes in the levels of MA and their metabolites in the central monoaminergic system in early postnatal ontogenesis in PM rats, which may contribute to the formation of behavioral and physiological abnormalities in adult PM rats. The growth of the PM amplitude and the increased severity of audiogenic seizures, observed during selection, confirms the connection between catatonic and neurological symptoms in this model — rats with pendulum-like hyperkinesis.