Alteration of Postural Reactions in Rats with Different Levels of Dopamine Depletion

Author:

Kalinina Daria S.123,Lyakhovetskii Vsevolod A.4ORCID,Gorskii Oleg V.145,Shkorbatova Polina Yu.134ORCID,Pavlova Natalia V.14,Bazhenova Elena Yu.14,Sysoev Yurii I.1346,Gainetdinov Raul R.1,Musienko Pavel E.147

Affiliation:

1. Institute of Translational Biomedicine, St. Petersburg State University Hospital, St. Petersburg State University, 199034 St. Petersburg, Russia

2. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 194223 St. Petersburg, Russia

3. Department of Neuroscience, Sirius University of Science and Technology, 354340 Sirius, Russia

4. Pavlov Institute of Physiology, Russian Academy of Sciences, 199034 St. Petersburg, Russia

5. Center for Biomedical Engineering, National University of Science and Technology “MISIS”, 119049 Moscow, Russia

6. Department of Pharmacology and Clinical Pharmacology, Saint Petersburg State Chemical and Pharmaceutical University, 197022 St. Petersburg, Russia

7. Life Improvement by Future Technologies Center “LIFT”, 143025 Moscow, Russia

Abstract

Dopamine (DA) is the critical neurotransmitter involved in the unconscious control of muscle tone and body posture. We evaluated the general motor capacities and muscle responses to postural disturbance in three conditions: normal DA level (wild-type rats, WT), mild DA deficiency (WT after administration of α-methyl-p-tyrosine—AMPT, that blocks DA synthesis), and severe DA depletion (DAT-KO rats after AMPT). The horizontal displacements in WT rats elicited a multi-component EMG corrective response in the flexor and extensor muscles. Similar to the gradual progression of DA-related diseases, we observed different degrees of bradykinesia, rigidity, and postural instability after AMPT. The mild DA deficiency impaired the initiation pattern of corrective responses, specifically delaying the extensor muscles’ activity ipsilaterally to displacement direction and earlier extensor activity from the opposite side. DA depletion in DAT-KO rats after AMPT elicited tremors, general stiffness, and akinesia, and caused earlier response to horizontal displacements in the coactivated flexor and extensor muscles bilaterally. The data obtained show the specific role of DA in postural reactions and suggest that this experimental approach can be used to investigate sensorimotor control in different dopamine-deficient states and to model DA-related diseases.

Funder

St. Petersburg State University, St. Petersburg, Russia

Russian Science Foundation

Grant of President of Russian Federation

State Program GP-47 “Scientific and Technological Development of the Russian Federation”

Ministry of Science and Higher Education of the Russian Federation

Publisher

MDPI AG

Subject

General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

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