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.