engleski

Evaluation of rotenone-induced dopaminergic striatal hypersensitivity

It has been proposed that stereotaxic injection of mitochondrial complex-I inhibitor rotenone into medial forebrain bundle mimics a slow neurodegenerative process found in idiopathic Parkinson's disease. We aimed to evaluate, if the development of unilateral dopaminergic striatal hypersensitivity, a hallmark of Parkinson's disease that develops due to severe chronic striatal dopamine depletion, may be revealed by characteristic apomorphine-induced contralateral rotations and by unilateral changes in the pattern of striatal gene expression characteristically observed in hemiparkinsonic models. Histomorphological inspection revealed rather extensive, but nonselective neurodegenerative changes at the rotenone injection site that in several animals resulted also in a total destruction of dopaminergic nigrostriatal neurons. Although we found several changes of gene expression patterns, that strongly indicated the development of striatal dopaminergic hypersensitivity, all but one of the animals that rotated contralateraly displayed either ipsilateral rotation or no turning bias. These results suggest a poor selectivity of stereotaxically applied toxin for dopaminergic neurons.

rotenone; dopamine; Parkinson's disease

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