The influence of low-molecular NGF mimetic dipeptide GK-2 behavior of mice from two outbred strains differing by brain weight

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Abstract

The investigation includes the analysis of nootropic effects of dimeric dipeptide, substance GK-2, nerve growth factor mimetic, in the cognitive test (elementary logic task) in mice of two strains selected for large and small relative brain weight (strains LB and SB). The influence of dipeptide (0.5 mg/kg, injected i.p., sub chronically) on cognitive test solution in mice of different genotypes had been opposite by “sign” — the proportion of mice, which solved the test successfully in LB strain was lower than that in controls, while it was higher in SB mice. It was also demonstrated that in neophagophobia test the dipeptide infusion induce more active reaction to the novel food with more clear cut reaction in LB mice. The data on genotype-dependent changes in behavior after GK-2 infusion are important for more extensive characteristic of GK-2 pharmacological properties as the plausible therapeutic drug.

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O. V. Perepelkina

Lomonosov Moscow State University

Email: ingapoletaeva@mail.ru
Russian Federation, Moscow

I. I. Poletaeva

Lomonosov Moscow State University

Author for correspondence.
Email: ingapoletaeva@mail.ru
Russian Federation, Moscow

P. Yu. Povarnina

Federal Center for Original and Perspective Technologies Investigations

Email: ingapoletaeva@mail.ru
Russian Federation, Moscow

T. A. Gudasheva

Federal Center for Original and Perspective Technologies Investigations

Email: ingapoletaeva@mail.ru
Russian Federation, Moscow

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2. Fig. 1. The mouse removes the plug that closes the hole in the dark compartment of the experimental chamber.

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3. Fig. 2. LP (s) of the solution of the test for searching for an entrance to a shelter in 3-month-old mice of the BM and MM lines in the first (open hole) and second (hole masked with wood shavings) presentations of the test. The data are presented as means and standard errors of the mean. Gray columns - administration of the dipeptide (5 days); black columns - control (administration of physiological solution); # - trend (p < 0.1), compared with the control groups of the same line (two-factor ANOVA, post hoc LSD-test according to Fisher).

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4. Fig. 3. LP (s) of the solution of the test for finding an entrance to a shelter in 8-month-old mice of the BM and MM lines in the first (open hole) and second (hole masked with wood shavings) presentations of the test. The data are presented as means and standard errors of the mean. Gray columns - administration of the dipeptide (single time), black columns - control (administration of physiological solution); * - significant (p < 0.05) difference from the same group of the MM line (two-factor ANOVA, post hoc LSD-test according to Fisher).

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5. Fig. 4. The proportions (%) of successful solutions in the shelter entrance search test in 8-month-old BM and MM mice with a hole closed with a plug (sum of two presentations). The data are presented as means. Gray bars — dipeptide administration, black bars — control (physiological solution administration); *** — significant (p < 0.001) difference from the same MM group; << — differences between the group after the dipeptide and the control group approach significance (Fisher's φ method, t = 1.8 and t =1.83, while p < 0.05 at t = 2.0).

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6. Fig. 5. Response to novel food in a novel (non-fearful) environment in BM and MM mice of two age groups exposed to the peptide (gray bars) and after administration of saline (black bars). Data are presented as means and standard errors of the mean. (a) — amount of cheese eaten by 3-month-old mice in 5 min. of the test; (b) — amount of cheese eaten by 8-month-old mice in 5 min. of the test; (c) — number of approaches by 3-month-old mice to the feeder with novel food; (d) — number of approaches by 8-month-old mice to the feeder with novel food; ** — statistically significant difference (p < 0.01) from the parameters of the corresponding control group (two-factor ANOVA, post hoc Fisher's LSD test).

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