This dissertation focuses on creating and applying an automated system for studying behavioral reactions and the effects of pharmacological agents (Memantine and Avandamet) in rats of different ages. The deterioration of brain functions in old rats can model age-related cognitive impairments in humans. A conditional food reflex (CFR) was used to assess higher nervous activity: expression and stability of the conditional reflex response, and the speed of its execution. The applied agents improved nervous activity parameters, contributing to developing methods for treating neurodegenerative diseases.
The system includes an electronic component and software for the microcontroller feeder, computer, and video recording of behavioral reactions. Its testing showed effectiveness in automated quantitative assessment of rat reactions. Temporal parameters (TP) of the conditional reflex serve as a direct measure of memory. TР reflect the speed of reflex execution and the stability of the reaction in the animal's memory. Increased reaction time may indicate memory deterioration, while reduction may indicate improvement. Analyzing the TP allows for the assessment of memory function. Studying changes in these parameters under the influence of agents helps evaluate their effect on memory and its impairments, which is important for treating neurodegenerative diseases such as Alzheimer's disease (AD).
Experiments were conducted on old and young rats. Old animals reproduce symptoms of nervous diseases: memory deterioration, cognitive impairments, and changes in motor reactions. This approach allows for studying the effectiveness of biologically active substances in restoring brain functions under conditions close to clinical situations. The results are important for treating dementia and neurodegenerative diseases.
The main results showed that the developed system allowed for obtaining numerical parameters for assessing the food conditional reflex in rats, aiding in understanding their behavior. Studies on the impact of the pharmacological agents on reflex and behavioral reactions of rats of different ages showed that memantine (MEM) significantly increased the success of the conditional reflex in old rats to the level of young ones, indicating memory improvement. Improvement in the analytical and synthetic activity of old rats after MEM administration may be associated with the potentiation of cortico-hippocampal pathways involved in memory formation.
The second part of the work studied the effect of MEM on motor reactions in rats of different ages and active and passive avoidance reactions. MEM positively affects motor activity and improves feeding and learning reactions in rats. It reduced the delay time of stepping down from the platform, making rats more decisive. MEM reduced hyper-emotionality, leading to fewer errors in the passive avoidance test, without impairing memory. MEM also increased locomotor activity, causing behavioral changes in the passive avoidance test, normalizing emotional and increasing motor excitability. TР of the conditional reflex, measured using the developed device, showed that MEM affected the success of food retrieval and the number of attempts to retrieve food between sound signals. It increased success and reduced the number of attempts. MEM did not affect the latent period or the time the paw stayed in the feeder window. TР of sensorimotor responses are informative indicators of CNS functional state and can be used to assess brain activity or pharmacological impacts on its functions.
According to the literature, glucose metabolism disorders or insulin resistance in diabetes can influence the development of neurodegenerative diseases like AD. Abnormalities in glucose metabolism and insulin levels can directly affect brain function and contribute to the development of pathological processes characteristic of AD. This provides a basis for studying drugs and treatment strategies to improve glucose processing and insulin levels in the brain to reduce the risk or slow the progression of neurodegenerative diseases.
The dissertation also studied the effect of Avandamet (AVD) on the CFR in rats, focusing on the relationship between the drug and cognitive functions in old animals. AVD is a combined drug containing metformin and rosiglitazone. Metformin reduces blood sugar levels, while rosiglitazone increases tissue sensitivity to insulin. AVD increases motor activity and the success of conditional reflex execution in old rats, which may be significant for treating neuronal diseases.
These studies are important for developing methods for assessing animal behavioral reactions and the possibilities of pharmacological influence on these reactions in the context of pathological conditions, particularly AD.
