The dynamics of nigrostriatal system damage and neurobehavioral changes in the rotenone rat model of Parkinson's disease

Abstract

Subcutaneous administration of rotenone to rats is currently a widely used method of reproducing Parkinson's disease (PD) symptoms, due to its convenience and effectiveness. Despite this, its influence on the temporal dynamics of parkinsonism development has yet to be investigated. The present study characterizes behavioral and neurochemical disruptancies underlying the dynamics of parkinsonism development in rats, induced by chronic subcutaneous administration of 2 mg/kg rotenone over the course of 18 days. In this article, the presence of two stages of pathology development in the model in question - the premotor and motor disability stages - are illustrated through a complex assessment of animal behavior, the development of an original neurological symptoms scale, and the establishment of the dynamics of histological and neurochemical changes in the brain. The premotor stage was observed up to 3 days of rotenone administration, and was characterized by a decrease in the motivational component of behavior, shown both in the food-getting task and in the "sucrose preference" test. A 30 % decrease in the number of cells in the substantia nigra pars compacta by the 3rd day of rotenone administration was also shown during the premotor stage. No changes in the metabolism of dopamine and other monoamine mediators were observed at this time. At the same time, acute administration of rotenone caused an increase in the GSH / GSSG ratio by 69 %. The motor stage developed after a decrease in the number of cells in the SNpc by more than 30 %, and was characterized by changes in the dopaminergic system, leading up to a 71 % reduction in dopamine levels in the striatum. It was shown that starting from 4 to 6 days of rotenone injection, experimental group animals begin to develop motor symptoms of Parkinson's disease, including bradykinesia, rigidity and postural instability. The development of motor impairment in all rats of this group was accompanied by significantly reduced activity of the antioxidant system in brain frontal lobe tissue homogenates, as compared to intact rats. Thus, in the used model of rotenone-induced parkinsonism, the dynamics of neuropathology development are described and the premotor stage of the disease is highlighted, which allows future using of this model in developing new approaches for treatment of parkinsonism at an early stage.

Keywords: Behavior; Catecholamines; Neurodegeneration; Parkinson’s disease model; Rat; Rotenone.