The intrastriatal 6-hydroxydopamine model of hemiparkinsonism: quantitative receptor autoradiographic evidence of correlation between circling behavior and presynaptic as well as postsynaptic nigrostriatal markers in the rat.
Unilateral injections of 6-hydroxydopamine into the striatum resulted in almost immediate ipsilateral amphetamine (AMPH)- and delayed contralateral apomorphine (APO)-induced circling behavior in rats. APO-induced rotation correlated positively with that caused by AMPH. In these animals, there was an almost complete disappearance of dopamine uptake sites as well as increases in DA D2 receptors in specific subdivisions of the ipsilateral caudate-putamen (CPu). Both the rate of AMPH- and APO-induced rotation correlated with the percentage of DA terminal loss in the total aspect and in various quadrants of the striatum. In contrast, AMPH- and APO-induced rotation correlated with the percentage increase in striatal D2 receptors only in the dorsolateral (DL) aspect of the CPu. These results indicate that both AMPH- and APO-induced rotation can be used to determine the extent of DA terminal loss in the rat basal ganglia. The positive correlation of circling behavior to only changes in DA D2 receptors observed in the DL striatal subdivision provides further evidence for the heterogeneity of the basal ganglia. This model of hemiparkinsonism in the rat which uses a distant intrastriatal approach to the destruction of nigral DA cell bodies may be a more appropriate model to study the regenerative properties of the nigrostriatal DA system. This approach could also be used to more specifically localize peptidergic receptors on midbrain dopamine cell bodies.
Cadet
J L
JL
Unit on Cellular and Molecular Neurotoxicology, NIDA, Baltimore, MD 21224.
Zhu
S M
SM
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001345:Autoradiography; D015415:Biomarkers; D003342:Corpus Striatum / Q000187:drug effects; D007150:Immunohistochemistry; D007267:Injections; D008297:Male; D008454:Mazindol / Q000378:metabolism / Q000494:pharmacology; D016627:Oxidopamine / Q000008:administration & dosage; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000473:pathology / Q000523:psychology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects*; D013134:Spiperone / Q000378:metabolism; D013239:Stereotyped Behavior / Q000187:drug effects*; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects
D015415:Biomarkers; D011954:Receptors, Dopamine; D013134:Spiperone; D016627:Oxidopamine; D008454:Mazindol; D000661:Amphetamine; D001058:Apomorphine