Correction of the wake-sleep cycle by intranasal administration of dopamine in modeling of the preclinical stage of Parkinson's disease in rats

Abstract

Sleep disorders, which are among the earliest and most sensitive non-motor manifestations of Parkinson's disease (PD), are not diagnosed in 40–50 % of patients and are not subject to the necessary correction. In this regard, the ineffectiveness of a late start of treatment, when more than 50 % of dopamine-producing neurons are already affected, dictates the need to search for and develop approaches to the prevention and slowdown of neurodegenerative pathology at the preclinical stages of its development using adequate experimental models. Taking into account the low bioavailability of dopamine (DA) and data on the advantages of the intranasal route of administration in comparison with oral and parenteral methods of drug delivery to the CNS, the aim of the work was to study the neurophysiological features of the wake-sleep cycle as early manifestations of nigrostriatal insufficiency and the effect of intranasal administration of DA on the quality of sleep during the formation of the preclinical stage of PD in rats. It was shown that under the conditions of modeling PD, the cyclic organization of sleep with a predominance of incomplete cycles against the background of hyperproduction of slow-wave sleep and REM phases are early manifestations of nigrostriatal insufficiency. Course administration of DA at a dose of 3 mg/kg is accompanied by the normalization of sleep quality in the form of reduction (by 76 %) in the number of incomplete cycles. The preventive orientation of the obtained effects may indicate a certain therapeutic potential of intranasal delivery of DA to the brain, aimed at slowing down the processes of neurodegeneration and possibly delaying its clinical manifestation