A 6-hydroxydopamine-induced selective parkinsonian rat model

Abstract

Previous parkinsonian rat models have generally been characterized by unilateral destruction of both the nigrostriatal pathway and the mesolimbic pathway using the neurotoxin 6-hydroxydopamine (6-OHDA). We created a hemiparkinsonian model in which there is 6-OHDA-induced destruction of the dopaminergic nigrostriatal pathway but sparing of the dopaminergic mesolimbic pathway. This resulted in reproducible, quantifiable rotational behavior in response to either amphetamine or apomorphine and a near total depletion of dopamine in the striatum ipsilateral to the lesion with a dorsolateral distribution of supersensitive dopaminergic D 2 receptors. This model parallels the MPTP (1-methy-4-phenyl-1,2,3,6-tetrahydropyridine)-induced hemiparkinsonian model in primates and more closely approximates the extent of neurodegeneration seen in human idiopathic Parkinson's disease than previous parkinsonian rat models. It may therefore prove a convenient model for studying the recently reported phenomenon of sprouting from host dopaminergic neurons following tissue implantation.