Effect of Intranasal Administration of Dopamine on Odor Perception in Rats with Nigrostriatal Dysfunction

Abstract

In recent years, there has been a growing interest in finding early predictors of Parkinson’s disease. In this regard, it is worth noting the olfactory dysfunction, which is associated with the death of neurons in the structures of the limbic system of the brain and a decrease in dopamine levels in the striatum. It was found that most patients with Parkinson’s disease have a clear olfactory dysfunction in the form of impaired differentiation and identification of odors. It has been suggested that the use of low doses of dopamine in the early stages of Parkinson’s disease will stop the progression of central nervous system disorders. The purpose of the study was to investigate the effect of intranasal administration of small doses of dopamine on the early manifestations of fine motor skills and olfactory sensory system function in nigrostriatal dysfunction in rats. Materials and methods. The experiments were performed on 2 groups of animals (n=14) with nigrostriatal dysfunction, which was modulated by partial bilateral electrical damage to the compact part of the substantia nigra. Stereotactic coordinates of the substantia nigra area were determined from the brain maps of rats by Fifkova and Marshall (quoted by Buresh), which corresponded to the distance from the point of intersection of the sagittal suture with bregma: F=5.5 mm, L=1.7 mm, H=9.0 mm. Rats of the first group (n=8) were intranasally administered with small doses of dopamine, and rats of the second group (n=6) were a comparison group. The fine motor skills of the forelimbs and the functional state of the olfactory system were studied when rats were presented with different odorants: emotionally positive (isovaleric acid) and emotionally negative (lemon essential oil) odorants. Results and discussion. The dynamics of the development of nigrostriatal dysfunction revealed a decrease in coordinated motor activity of the forelimbs, muscles of the oral pole and tongue and increased olfactory sensitivity to emotionally negative odorant (lemon essential oil) and loss of 40% of animals’ olfactory sensitivity to emotionally positive isovaleric odor. Conclusion. Prolonged intranasal administration of low doses of dopamine for 10 days to rats with nigrostriatal dysfunction resulted in a 26.2% increase in the activity of fine motor skills of the forelimbs, oral poles and tongue. In these rats, recovery of olfactory sensitivity to the perception of the smell of emotionally negative odorant was found. The action of the emotionally positive stimulus of isovaleric acid revealed an increase in olfactory sensitivity in 75% of animals to the level of baseline values and a decrease in the threshold of sensitivity to it, which was reflected in an increase in the number of approaches and time of odorant research