Paradoxical sleep deprivatory effect of a single low dose of MPTP which did not produce dopaminergic cell loss

Abstract

In a previous study, we reported on a selective and long-lasting paradoxical sleep (PS) deprivation in cats following repeated administration of the Parkinson syndrome-inducing neurotoxin N-methyl-4-pheny11,2,3,6-tetrahydropyridine (MPTP). While the characteistic motor deficits occurred only from the 2^nd to 3^rdday of a 5-day long administration of 5 mg/kg per day MPTP i.p., the PS deprivation started immediately after the first injection and lasted altogether for 11–13 days. The motor deficiencies induced by repeated administration of MPTP are mainly due to the selective depletion of dopaminergic neurons in the nigrostriatal system as the histological and biochemical data show. The immediate onset of PS deprivation and the PS recovery, despite the definite cell loss, suggests a mechanism independent of cell destruction. In our present study we investigated the occasional histological and the PS-deprivatory effect of a single low dose of MPTP in cats. A single injection of 2 mg/kg MPTP i.p. resulted in PS deprivation lasting for 2.5–3.5 h. The duration of other sleep stages showed no significant change and PS recovery was without rebound phenomenon, as in the case of repeated administration. Even a higher single dose of MPTP (5 mg/kg) resulted in no visibly detectable nigrostriatal cell loss. We suggest that the changes in monoamine release and/or turnover are involved in the PS deprivatory effect of MPTP.