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Vol. 22, Art. 28 (pp. 404-425)    |    2021       

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Comparative analysis of modifications of the conditioned passive avoidance reflex test on sensitivity of scopolamin-induced amnesia detection in rats

Konovalov A.V., Yudin M.A., Chepur S.V., Buzmakova A.L., Potapova A.V., Subbotina S.N.

Federal State Budgetary Institution "State Research Testing Institute of Military Medicine" of the Ministry of Defense of the Russian Federation

Federal State-Funded Educational Institution of Higher Professional Education North-Western State Medical University named after I.I. Mechnikov (NWSMU), Ministry of Health of the Russian Federation

Brief summary

Nowadays the treatment of Alzheimer's disease, accompanied by the progression of cognitive impairment, and the problem of sufficiency of its modeling in the experiment in the search for effective drugs represent unsolved medical, theoretical and practical problems. The choice of conditioned passive avoidance reflex (CPAR) amnesia model in preclinical studies can strongly influence the observed biological responses and integral indicators. In this regard, a more profound study of the issue of experimental modeling of amnesia can improve the quality and reliability of experimental results. The use of scopolamine for the induction of short-term and long-term memory impairments in rodents is widespread. The comparison of sensitivity of various modifications of passive avoidance reaction test, simulating anterograde and retrograde amnesia with intravenous administration of scopolamine in the dose range 0,5 - 20 mg/kg was made. With regard to short-term memory the most sensitive was the model of anterograde amnesia, which was induced by the administration of scopolamine for 30 min at doses exceeding 1 mg/kg. The sensitivity of this technique was confirmed by statistically significant changes in effective doses of the model drug, the proportion of animals with amnesia, and the average time spent in the light chamber. In relation to long-term memory the model of anterograde amnesia was also recognized as the most sensitive. Administration of scopolamine at doses 1 - 2,5 mg/kg 24 h following electric pain stimulation led to statistically significant differences in the mean time spent by rats in the light chamber. Among the models of retrograde amnesia modification of the passive avoidance reflex test with repeated reminder was more sensitive than modification without reminding. The minimum value of the dose of scopolamine, that caused statistically significant changes in test parameters, in the model with repeated reminder was 10 mg/kg, while when using the model without a reminder, the administration of a cholinergic antagonist at a dose of 20 mg/kg turned out to be effective.


Key words

Alzheimer's disease, scopolamine, retrograde amnesia, anterograde amnesia

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25. Bon' E.I., Zimatkin S.M. The structure and development of the rat hippocampus. Zhurnal Grodnenskogo gosudarstvennogo meditsinskogo universiteta 2018; 16 (2): 132-138.


26. Buchanan K.A., Petrovic M.M., Chamberlain S.E-L., Marrion N.V., Mellor J.R. Facilitation of long-term potentiation by muscarinic M1 receptors is mediated by inhibition of SK channels. Neuron. 2010; 68: 948-963.


27. Catterall W.A., Wisedchaisri G., Zheng N. The chemical basis for electrical signaling. Nat. Chem. Biol. 2017; 13 (5): 455 463.


28. Cui E.D., Strowbridge B.W. Selective attenuation of Ether-a-go-go related K(+) currents by endogenous acetylcholine reduces spike-frequency adaptation and network correlation. Elife. 2019; 8: e44954.


29. Robinson L, Platt B, Riedel G. Involvement of the cholinergic system in conditioning and perceptual memory. Behav Brain Res. 2011; 221 (2): 443-465.


30. Nomura, Y., Nishiyama, N., Saito, H., Matsuki, N. Role of cholinergic neurotransmission in the amygdala on performances of passive avoidance learning in mice. Biological & Pharmaceutical Bulletin. 1994; 17: 490-494.