Комбинация дипептида PRO-GLY и МК-801 облегчает процессы неассоциативного обучения в условиях слабого стресса при групповой актометрии

Abstract

Abstract. Oxytocin (OT) is a neuropeptide that not only plays a hormonal role, but also modulates cognitive functions. OT in vitro reduced the activity of N-methyl-D-aspartate (NMDA)-type glutamate receptors, thereby influencing one of the main neurotransmitter mechanisms modulating learning and memory processes. Taking into account the above, it was of interest to evaluate the interaction of the Pro-Gly dipeptide, structurally related to the OT fragment (Pro-Leu-Gly-NH2), and MK-801 (dizocilpine, a non-competitive antagonist of N-methyl-D-aspartate receptors). The purpose of the study was to study the effect of Pro-Gly dipeptide in combination with M-801 and without it on the processes of non-associative learning in mice. In experiments on 280 outbred male ICR mice, studies of the substance Pro-Gly. BCBV9787 and substances MK-801 hydrogen maleate (M107-50MG), p. 078K4606 manufactured by Sigma-Aldrich, USA. 28 experimental groups were formed, the number of animals in each group was 10. The experimental groups included: control-1 (C-1), intact – 12 groups; control-2 (K-2), “injection stress”: introduction of a solvent – 4 groups; main groups 1-3: administration of Pro-Gly (0.5 mg/kg, i.p.) + solvent – 4 groups; Pro-Gly (0.5 mg/kg, i.p.) + MK-801 (0.05 mg/kg, i.p.) – 4 groups; MK-801 at a dose of 0.05 mg/kg i.p. + solvent – 4 groups. Vertical motor activity (VLA) was measured for 30 minutes using a multichannel actometer “Activity Cages” (Ugo Basile, Italy). We compared mobility in the first 5 minutes and in the last 5 minutes of group actimetry (10 individuals at a time). In K-1, well-defined habituation processes were noted (p < 0.05). Under conditions of mild “injection” stress, mice in control group 2 (K-2) showed sharp disturbances in the habituation process. Pro-Gly and MK-801, administered separately, did not prevent stress-related impairments in non-associative learning. At the same time, the combination of Pro-Gly (0.5 mg/kg, i.p.) and MK-801 (0.5 mg/kg, i.p.) statistically significantly corrected stress-impaired non-associative learning processes.