The nigrostriatal pathway is very likely involved in sleep regulation, considering the occurrence and high
prevalence of sleep-related disorders in patients with Parkinson’s disease. Indeed, dopaminergic neurons in the ventral
tegmental area were recently shown to fire in bursts during paradoxical sleep (PS), but little is known about the activity of
the nigrostriatal dopamine (DA) cells in relation to PS. In view of that we hypothesized that paradoxical sleep deprivation
(PSD) may play a relevant role in nigrostriatal tyrosine hydroxylase (TH) expression and, subsequently, in sleep rebound.
The present study was designed to determine the effects of PSD in the nigrostriatal pathway in mice by means of
neurochemical and behavioral approaches. Intraperitoneal reserpine (1 mg/kg) associated to α-methyl-p-tyrosine (αMT)
(250 mg/kg) to produce catecholamine depletion, or rotenone (10 mg/kg) to increase striatal DA turnover were injected 30
min before the 24 h of PSD. Catalepsy and open-field tests indicated that motor deficits induced by reserpine-αMT were
counteracted by PSD, which, in contrast, potentiated the motor impairment induced by rotenone. Besides, PSD produced
down-regulation on TH expression within the substantia nigra pars compacta and striatum, without affecting the number
or the optical density of dopaminergic neurons present in the respective areas. Interestingly, PSD potentiated the downregulation
of TH expression in the substantia nigra pars compacta and striatum induced by the co-administration of
reserpine-αMT. These results reinforce the notion of a strong participation of DA in PS, as a consequence of the
modulation of TH protein expression in the nigrostriatal pathway.