Abstract—We studied the dopamine-, serotonin-, and norepinephrinergic systems in various brain structures of BALB/c male mice on days 15, 42, and 64 of postnatal development (PND) in the model of autism spectrum disorder induced by sodium valproate administration (400 mg/kg, s/c) to pregnant females. It was found that the level of both catechol- and indolamines in the brain structures of control 15-day-old mice is considerably lower than in 64-day-old adult animals. Prenatal administration of sodium valproate (SV) caused a decrease in all parameters of monoaminergic neurotransmission in the striatum of mouse offspring aged 15 days but did not lead to neurochemical changes in other studied brain structures. By PND 42, the general pattern of changes in neurotransmitter concentrations did not differ from the developmental dynamics of neurotransmitter system maturation in the control group. The level of DA kept increasing and by PND 64, did not differ from controls. The parameters of serotonergic system changed similarly, with the peak serotonin concentration by PND 42 and a significant decrease by PND 64, whereas the level of 5-HIAA in the striatum increased gradually with maximum differences observed by PND 64. Thus, the data obtained suggest that administration of SV to pregnant females affects the activity of the dopamine- and serotonergic brain systems in the progeny, inducing its decrease in the striatum by PND 15 followed by recovery to control level by PND 64.
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The work was performed within the scope of state program for the Zakusov Institute of Pharmacology (State Assignment no. 0521-2019-0007: Developing treatments for epilepsy, Parkinson’s disease, and autism based on new data on the pathogenesis of the indicated diseases).
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Conflict of interests. The authors declare no conflicts of interest.
Ethical approval. Organizing and conducting experiments were in compliance with “Rules of good laboratory practice of the Russian Federation” approved by the Order of the Ministry of Health of the Russian Federation № 199 of April 1, 2016. The animals were kept in accordance with SP 2.2.1.3218-14 “Sanitary and epidemiological requirements to arrangement, equipment and maintenance of biological clinics (vivariums)” of August 29, 2014. The experimental procedures were approved by the Bioethics Commission of the FSBSI “Research Institute of Pharmacology Named after V. V. Zakusov” (protocol no. 6 of April 16, 2018).
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Kudrin, V.S., Narkevich, V.B., Alymov, A.A. et al. Dysfunction of the Monoaminergic Brain System in BALB/c Mice Progeny after Sodium Valproate Administration to Pregnant Females: Neurochemical Study. Neurochem. J. 15, 59–64 (2021). https://doi.org/10.1134/S1819712421010062
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DOI: https://doi.org/10.1134/S1819712421010062