Changes in Motor Activity and the Sleep–Waking Cycle in an MPTP Model of Parkinson’s Disease in Mice

Abstract

Mice with previously implanted electrodes for recording the cortical electroencephalogram and electromyograms underwent all-day baseline videopolysomnography with a 12/12 light cycle, after which animals received doses of 24 or 48 mg/kg of the neurotoxin precursor MPTP (1-methyl-4-phenyl-1.2.3.7-tetrahydropyridine) or physiological saline (controls) and recording was continued for 14 days. At the end of the experiments, morphological monitoring of the extent of lesions to the dopaminergic system was performed. Increases in motor activity and the total duration of waking during the dark part of the night were seen after administration of MPTP, as compared with controls. These changes were accompanied by decreases in the durations of rapid and (at the level of a tendency) slow-wave sleep. These changes were apparent by recording day 7 and were significant by day 14; they were more marked after treatment at a dose of 48 mg/kg than after the smaller dose. No changes were seen during the light period of the day. Morphological monitoring demonstrated a 70% reduction in the number of dopamine-containing neurons in the compact zone of the substantia nigra after administration of MPTP (48 mg/kg) and a 35% drop after MPTP (24 mg/kg).