IMPAIRMENTS OF COGNITIVE FUNCTIONS IN THE MODEL OF THE PRECLINICAL STAGE OF PARKINSON'S DISEASE IN WISTAR RATS

The preclinical stage of Parkinson's disease (PD) when brain preserves the most amount of dopaminergic neurons in the nigrostriatal system and the compensatory mechanisms are not exhausted is of the most powerful "therapeutic window". Therefore, for the last years a particular emphasis is focused on a search of early markers of neurodegenerative process and a development of experimental models. The aim of the study was to detect early behavioral changes reflecting disorders in cognitive functions and emotionality in a rat model of the premotor stage of PD and to elicit the most informative tests. A rat model of the prolonged (up to 21-t day) preclinical stage of PD was developed in the laboratory on the basis of the enhancing decline in the ubiquitin-proteasome system of the brain induced by a double intranasal injection of specific proteasome inhibitor lactacystin. The new object recognition test, the Y-maze test and the "what - where - when" paradigm was used to assess cognitive dysfunctions. The open field test and the elevated plus maze test were used to asses anxiety. The lactacystin administration was found to impair spatial memory, episodic memory, and new object recognition in rats against a background of a transitory increase in the level of anxiety. The data obtained suggests that the disorders in cognitive functions and emotionality can be early features of the development of neurodegeneration in the brain.