Sleep disturbances in the rotenone animal model of Parkinson disease

Abstract

Parkinson disease (PD) is characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc) and the presence of intracytoplasmatic inclusions known as Lewy bodies. Chronic administration of rotenone (RT) produces Parkinson's-like symptoms in rats. Because PD patients have disrupted sleep patterns, we determined if chronic RT administration produces similar changes in rat sleep. RT was administered for 28 days to rats. Basal and vehicle (VH) rats received saline or dimethyl sulfoxide and polyethylene glycol (1:1), respectively. VH infusion induced a progressive decrease in non-rapid eye movement sleep (NREMS) during the 4-week period of VH infusion and REMS was reduced in the third and fourth week of VH infusion. VH infusion did not induce dopaminergic cell degeneration. Rats receiving RT infusion also showed decreased NREMS during the treatment. REMS was dramatically reduced on day 7 although subsequently on days 13 and 20 REMS was similar to basal values. After 4 weeks of RT infusion, time in REMS was decreased again. In RT-treated rats, progressive dopaminergic cell degeneration occurred in the SNc. After 4 weeks of daily injections of l-dopa in RT-infused rats, NREMS values remained similar to those values obtained after RT alone. l-dopa therapy did, however, induce a recovery of REMS in weeks 3 and 4 of RT infusion. Dopaminergic cell damage persisted in the l-dopa-RT-infused rats. We conclude that the RT-PD rat model is associated with large long-term sleep disruption, however, the vehicle, DMSO/PEG had as large an effect as RT on sleep, thus changes in sleep cannot be ascribed to loss of dopaminergic cells. Such results question the validity of the RT-PD rat model.