The pesticide rotenone has been shown to cause systemic inhibition of 
mitochondrial complex I activity, with consequent degeneration of dopamine 
neurons along the nigrostriatal pathway, as observed in Parkinson's disease 
(PD). Recently, intracranial infusion of rotenone was found to increase the 
protein levels of the Lewy body constituents, α-synuclein and small 
ubiquitin-related modifier-1(SUMO-1), in the lesioned hemisphere of the mouse 
brain. These findings are supportive of a mouse model of PD, but information 
about the dopamine-synthesizing enzyme, tyrosine hydroxylase (TH), an essential 
marker of dopaminergic status, was not reported. Clarification of this issue is 
important because an intracranial rotenone mouse model of Parkinson's disease 
has not been established. Towards this end, the present study examined the 
effects of intracranial rotenone treatment on TH and α-synuclein 
immunohistochemistry in addition to forelimb motor function. Mice were 
unilaterally infused with either vehicle or rotenone (2μg/site) in both the 
medial forebrain bundle and the substantia nigra. The forelimb asymmetry 
(cylinder) test indicated a significant decrease in use of the contralateral 
forelimb in lesioned animals as compared to the sham group. Densitometric 
analysis revealed a significant depletion of TH immunofluorescence within the 
ipsilateral striatum and substantia nigra of lesioned animals. Moreover, a 
significant bilateral increase in α-synuclein immunofluorescence was found in 
the substantia nigra of lesioned mice, as compared to control animals. These 
findings indicate that this intracranial rotenone mouse model will be useful for 
studies of neurodegenerative disorders such as PD.