A 6-hydroxydopamine-induced selective parkinsonian rat model.
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 D2 receptors. This model parallels the MPTP (1-methyl-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.
Perese
D A
DA
Surgical Neurology Branch, NINCDS, Bethesda, MD 20892.
Ulman
J
J
Viola
J
J
Ewing
S E
SE
Bankiewicz
K S
KS
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001345:Autoradiography; D004195:Disease Models, Animal; D007839:Functional Laterality / Q000502:physiology*; D006892:Hydroxydopamines; D008032:Limbic System / Q000503:physiopathology*; D008297:Male; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D017448:Receptors, Dopamine D2; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology*
D006892:Hydroxydopamines; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D016627:Oxidopamine; D000661:Amphetamine; D001058:Apomorphine