Effect of dopaminergic substances on sleep/wakefulness in saline- and MPTP-treated mice.

Sleep/wakefulness (S/W) disorders are frequent in Parkinson's disease (PD). The underlying causes have yet to be elucidated but dopaminergic neurodegenerative lesions seem to contribute to appearance of the disorders and anti-Parkinsonian medication is known to accentuate S/W problems. Hence, we reasoned that studying the acute effect of dopaminergic compounds on S/W in an animal model of PD might improve our knowledge of S/W regulation in the context of partial dopaminergic depletion. To this end, we tested the effect of levodopa (l-dopa), pergolide (a mixed D(2)/D(1) agonist) and lisuride (a D(2) agonist) on S/W recordings in MPTP-treated mice, in comparison with controls. Our results showed that dopaminergic compounds modify S/W amounts in both control and MPTP mice. Wakefulness amounts are greater in MPTP mice after l-dopa (50 mg kg(-1)) and lisuride (1 mg kg(-1)) injections compared with control mice. Moreover, the paradoxical sleep latency was significantly longer in MPTP mice after high-dose l-dopa administration. Our observations suggest that the actions of both l-dopa and lisuride on S/W differ slightly in MPTP mice relative to controls. Hence, MPTP-induced partial DA depletion may modulate the effect of dopaminergic compounds on S/W regulation.

The effects of serotoninergic, noradrenergic, cholinergic and dopaminergic drugs on vigilance states in MPTP-treated mice.

Sleep/wakefulness disorders are frequent in Parkinson's disease. Although the causes have yet to be established, it is known that dopaminergic neuronal lesions modulate paradoxical sleep (PS) regulation structures containing serotonin, noradrenaline and acetylcholine. Our previous vigilance state studies have revealed an increase in the amount of PS over the nyctohemeral period in the MPTP-treated mouse model of Parkinson's disease. The aim of the present work was to compare the effect of drugs modulating serotonin (citalopram), noradrenaline (desipramine), acetylcholine (arecoline) and dopamine (GBR 12909) neurotransmission on sleep/wakefulness patterns in MPTP mice and control mice. Citalopram reduced the amount of PS in MPTP and control mice to the same extent. Desipramine also induced a PS reduction, which was less pronounced in MPTP mice than in control mice. Arecoline increased the amount of PS in MPTP mice but not in controls. GBR 12909 induced a PS reduction (for the highest dose) more pronounced in MPTP mice than in control animals. Given that the responsiveness of MPTP mice differs markedly from that of controls, our study suggests that MPTP can alter sleep/wakefulness neurotransmission systems. Dysfunction of the latter may be responsible for PS disorders in MPTP mice.

Vigilance states in a parkinsonian model, the MPTP mouse.

Sleep disturbances and vigilance disorders are frequently observed in Parkinson's disease. Despite the fact that the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse is one of the best-known animal models of Parkinson's disease, sleep analysis has never previously been performed in this system. In the present study, we explored sleep-wakefulness cycles in MPTP-treated mice and compared the results to data from untreated mice. MPTP (25 mg/kg) was injected daily for 5 days. After recovery, polysomnography was recorded over 48 h. Dopaminergic lesions of the substantia nigra and striata were evaluated using immunohistochemical markers. Immunohistochemical analysis showed a loss of dopaminergic neurons in MPTP mice. Compared with controls, MPTP-treated mice presented changes in sleep architecture throughout the nycthemeral period, with longer wakefulness and paradoxical sleep episodes and an increase in the amount of paradoxical sleep. We observed changes in sleep architecture in MPTP-treated mice, compared with saline-treated mice. MPTP mice show more consolidated vigilance states with higher amount of paradoxical sleep than controls. Although the MPTP-treated mouse is not a good model of sleep disturbances in PD, our results suggest that it could be a good pharmacological model for studying the effects of dopaminergic treatments on animal sleep-wakefulness cycles.