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Neurochemical Effects of Afobazol on the Level of Monoamines and Their Metabolites in Mice with Various Emotional Phenotypes with Serotonin Deficit

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Abstract—We studied the neurochemical effects of afobazol in the brain structures of BALB/C and C57BL/6 mice with serotonin deficit induced by para-chlorophenylalanine (PCPA), which inhibits tryptophan 5‑hydroxylase, the main enzyme of serotonin synthesis. Interstrain differences were found in the level of norepinephrine (NE), serotonin (5-HT), and dopamine (DA) metabolism parameters in the frontal cortex (FC), amygdala, striatum, hypothalamus, and hippocampus. It was demonstrated that PCPA (350 mg/kg/3 days) caused a considerable decrease in the level of 5-HT and its metabolite 5-HIAA in the structures of the brain studied in both strains of mice, but in BALB/C mice the decrease in these indices was more intense (2–2.5 times). PCPA decreased the level of NE in the hypothalamus, amygdala, and striatum of C57BL/6 mice. In the 5-HT deficiency model, afobazol (5 mg/kg) influenced the parameters of dopaminergic neurotransmission by decreasing the level of DOPAC and the DOPAC/DA ratio in the hypothalamus and striatum of both strains. An increase in the content of 5-HT and NE was observed after a decrease caused by the administration of PCPA in the hypothalamus and amygdala of BALB/C mice and the hippocampus and amygdala of C57BL/6 mice. The indices of 5-HIAA/5-HT metabolism rate were decreased. The results of the current study confirm the previous data on the role of the serotonergic brain systems in the mechanism of action of afobazol. In PCPA-induced serotonin deficit, the drug influenced both stress-resistant (C57BL/6) and more emotionally labile animals (BALB/C) which is reflected by the restoration of serotonin and norepinephrine levels in the hypothalamus of BALB/C mice, as well as in the amygdala and hippocampus of C57BL/6 strain.

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Funding

The work was supported by the 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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  1. Zakusov Institute of Pharmacology, ul. Baltiiskaya 8, 125315, Moscow, Russia

    V. B. Narkevich, S. A. Litvinova, V. S. Rogovskii, I. B. Tsorin & V. S. Kudrin

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  1. V. B. Narkevich
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  2. S. A. Litvinova
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  3. V. S. Rogovskii
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  4. I. B. Tsorin
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  5. V. S. Kudrin
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Correspondence to V. B. Narkevich.

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Conflict of interests. The authors declare no conflicts of interest.

Ethical approval. Experiments were performed 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 maintained 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 Zakusov Institute of Pharmacology , (protocol no. 6 of April 16, 2018).

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Narkevich, V.B., Litvinova, S.A., Rogovskii, V.S. et al. Neurochemical Effects of Afobazol on the Level of Monoamines and Their Metabolites in Mice with Various Emotional Phenotypes with Serotonin Deficit. Neurochem. J. 15, 65–70 (2021). https://doi.org/10.1134/S1819712421010086

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