E.V. Loseva – Dr.Sc. (Biol.), Chief Research Scientist, Laboratory of Functional Neurocytology,  Institute of Higher Nervous Activity and Neurophysiology RAS (Moscow) E-mail: losvnd@mail.ru 

N.A. Loginova – Ph.D. (Biol.), Senior Research Scientist, Laboratory of Functional Neurocytology, 

Institute of Higher Nervous Activity and Neurophysiology RAS (Moscow)

E-mail: nadezhda.loginova1982@gmail.com

L.I. Russu – Research Scientist, Laboratory of Tissue Cultures, D.I. Ivanovskii Institute of Virusology, Gamaleya

Federal Research Center for Epidemiology and Microbiology, Ministry of Health of the Russian Federation (Moscow)  E-mail: plano77@bk.ru 

M.V. Mezentseva – Dr.Sc. (Biol.), Head of the Laboratorhy of Tissue Cultures, D.I. Ivanovskii Institute 

of Virusology, Gamaleya Federal Research Center for Epidemiology and Microbiology,  Ministry of Health of the Russian Federation (Moscow)  E-mail: marmez@mail.ru

A set of rat behavioral parameters in the "elevated plus-maze" test (EPM) after 4-fold daily intranasal injection of Single Wall Carbon Nanotubes (SWСNT) 100 µl suspension in a middle dose (52 µg/kg) was compared with the behavior of rats after intranasal injection of saline in the same volume (control). It has been shown that under the influence of SWCNT, some behavioral disorders occur. Thus, in the group of rats receiving SWCNT, the number of visits to open arms increases, as well as the total and average time of stay in them. At the same time, in the SWCNT group with a high level of significance (p <0.001), the latent period of entry into the closed arm increases, but the latent period of entry into the open arm decreases. This is due to the fact that rats receiving nanotubes at first go into the open arm directly from the central area, without going into the closed arm, as most control animals do. They spend time mainly in the square of the open arm nearest to the center, but when they get into the closed arm they no longer go into the open arm until the end of the experiment. This is evidenced by a greater number of visits to nearby squares in the open arms, as well as the same latent period of the first visit the closed arm and the total time spent in the open arms. In addition, in rats under the influence of SWCNT increases the number, total and average time of freezing, while in control rats the freezing is not observed.

These data indicate that in rats under the influence of a middle dose of SWCNT, the time for taking an adequate decision to enter the closed arm increases in order to avoid a stressful situation (bright light, height) in the open arm of the EPM. In addition, apparently, these animals experience stress in the installation of EPM more than in control. It is assumed that small SWCNTs can penetrate into the brain after intranasal administration, and due to their properties (increased strength, super electrical and thermal conductivity), they lead to neurodegenerative processes in the structures responsible for the decision-making mechanism. In this case, the structures reactive to stress may also suffer. A further morpho-functional study of these structures will help confirm or disprove this assumption.

1. Fathutdinova L.M., Haliullin T.O., SHvedova A.A. Ocenka riska zdorov'yu pri vozdejstvii uglerodnyh nanotrubok: ot toksikologii k ehpidemiologicheskim issledovaniyam (obzor sovremennogo sostoyaniya problemy) // Rossijskie nanotekhnologii. 2015. T. 10. № 5–6.   S. 144–150.
2. Gmoshinskij I.V., Hotimchenko S.A., Giger N.A., Nikityuk D.B. Uglerodnye nanotrubki: mekhanizmy dejstviya, biologicheskie markery i ocenka toksichnosti in vivo (obzor literatury) // Gigiena i sanitariya. 2017. T. 96. № 2. S. 176–186.
3. D'yachkov P.N. EHlektronnye svojstva i primenenie nanotrubok [EHlektronnyj resurs]. 2-e izd. (ehl.). M.: BINOM. Laboratoriya znanij. 2012. 488 s. (Nanotekhnologii). http://files.lbz.ru/pdf/cC1096-8-ch.pdf 
4. Sayapina N.V., Sergievich A.A., Batalova T.A., Novikov M.A., Asadcheva A.N., CHajka V.V., Golohvast K.S. EHkologicheskaya i toksikologicheskaya opasnost' uglerodnyh nanotrubok: obzor rossijskih publikacij // Izv. Samarskogo nauchnogo centra Rossijskoj akademii nauk. 2014. T. 16. № 5(2).  S. 949–953.
5. Rahman L., Jacobsen N.R., Aziz S.A., Wu D., Williams A., Yauk C.L., White P., Wallin H., Vogel U., Halappanavar S. Multi-walled carbon nanotubeinduced genotoxic, inflammatory and pro-fibrotic responses in mice: Investigating the mechanisms of pulmonary carcinogenesis // Mutat Res. 2017. V. 823. P. 28–. doi: 10.1016/j.mrgentox.2017.08.005.
6. Sayapina N.V., Sergievich A.A., Kuznetsov V.L., Chaika V.V., Lisitskaya I.G., Khoroshikh P.P., Batalova T.A., Tsarouhas K., Spandidos D., Tsatsakis A.M., Fenga C., Golokhvast K.S. Influence of multi-walled carbon nanotubes on the cognitive abilities of Wistar rats // Exp. Ther. Med. 2016. V. 12. № 3. P. 1311–1318.
7. Loseva E.V., Mezenceva M.V., Russu L.I., Loginova N.A., Panov N.V., SHCHetvin M.N., Suetina I.A. Podavlenie sinteza citokinov v selezenke i mozge i slabye izmeneniya ehkspressii c-fos v mozge u krys pri intranazal'nom vvedenii odnoslojnyh uglerodnyh nanotrubok // Rossijskie nanotekhnologii. 2016. T. 11. № 3–4. S. 80–86. 
8. Md S., Mustafa G., Baboota S., Ali J. Nanoneurotherapeutics approach intended for direct nose to brain delivery // Drug Dev. Ind. Pharm. 2015.  V. 41. № 12. P. 1922–1934. doi: 10.3109/03639045.2015.1052081. 
9. Loseva E.V., Loginova N.A., Russu L.I., Mezenceva M.V. Rezul'taty izmereniya parametrov povedeniya krys pri intranazal'nom popadanii v organizm maloj dozy odnoslojnyh uglerodnyh nanotrubok // Nejrokomp'yutery: razrabotka, primenenie. 2017. № 7. S. 52–55.
10. Loseva E.V., Loginova N.A., Sarkisova K.YU., Russu L.I., Mezenceva M.V. Izmerenie povedencheskih pokazatelej u krys v testah na trevozhnost' i depressiyu pri ostrom intranazal'nom vvedenii vzvesi odnoslojnyh uglerodnyh nanotrubok v maloj doze // Biomedicinskaya radioehlektronika. 2017.  № 10. C. 62–72.
11. Pellow S., Chopin P., File S.E., Briley M. Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat // J. Neurosci. Meth. 1985. V. 14. P. 149–167.
12. Samotrueva M.A., Teplyj D.L., Tyurenkov I.N. EHksperimental'nye modeli povedeniya // Estestvennye nauki. 2009. T. 27. № 2. S. 140–152.
13. Voronina T.A., Garibova T.L, Krajneva V.A. Povedencheskie ehksperimental'nye modeli depressii // Farmakokinetika i Farmakodinamika. 2017. № 3. PDF. 1439 http://www.pharmacokinetica.ru/articles/item/povedencheskie-eksperimentalnye-modeli-depressii 
14. Funahashi S. Prefrontal contribution to decision-making under free-choice conditions // Front Neurosci. 2017. № 11. P. 431. Published online 2017 Jul 26. doi: 10.3389/fnins.2017.00431
15. Amemori K., Amemori S., Gibson D.J., Graybiel A.M. Striatal microstimulation induces persistent and repetitive negative decision-making predicted by striatal beta-band oscillation. Neuron. 2018. V. 99. Is. 4. P. 829–841. DOI: https://doi.org/10.1016/j.neuron.2018.07.022 
16. Stopper C.M., Floresco S.B. What's better for me? Fundamental role for lateral habenula in promoting subjective decision biases // Nature Neuroscience. 2014. V. 17. P. 33–35.