Motor effects and mapping of cerebral alterations in animal models of Parkinson's and Huntington's diseases.
Changes in stimulant-induced behavioral effects and subcortical c-Fos expression were compared between rodent models of Parkinson's disease (PD) and Huntington's disease (HD). Rats received either a unilateral 6-hydroxydopamine (6-OHDA)-induced lesion of the nigrostriatal dopamine pathway (PD model) or a unilateral infusion of antisense oligodeoxynucleotides targeting c-fos into the striatum (HD model). Dopamine-lesioned animals received intraperitoneal injections of either d-amphetamine (6-OHDAamp group) or apomorphine (6-OHDAapo group), whereas all animals that received antisense infusions received d-amphetamine (ASF group). All groups exhibited robust circling behavior upon stimulant challenge. Changes in subcortical activation, as assessed by the induction of Fos-like immunoreactivity (Fos-LI), were examined in several brain regions. The 6-OHDAamp and ASF groups exhibited robust, ipsiversive circling behavior, with similar changes in Fos-LI in the striatum, entopeduncular nucleus, superior colliculus, and ventromedial thalamus. The 6-OHDAapo group exhibited contraversive rotation and had reciprocal patterns of Fos-LI in these regions. Despite exhibiting the same direction of rotation, the 6-OHDAamp and ASF groups had markedly different patterns of Fos-LI in the globus pallidus and the pontine reticular formation. These results suggest that the globus pallidus may undergo distinct alterations in PD and HD and that the pontine reticular formation is particularly susceptible to changes in mesencephalic dopamine sources.
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
M O
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Hebb
H A
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Robertson
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000378:metabolism / Q000503:physiopathology*; D001931:Brain Mapping; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D003913:Dextroamphetamine / Q000494:pharmacology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D005260:Female; D006816:Huntington Disease / Q000503:physiopathology*; D008297:Male; D009043:Motor Activity / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D016627:Oxidopamine / Q000494:pharmacology; D010300:Parkinson Disease / Q000503:physiopathology*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D014018:Tissue Distribution / Q000502:physiology
D016376:Oligonucleotides, Antisense; D016760:Proto-Oncogene Proteins c-fos; D016627:Oxidopamine; D003913:Dextroamphetamine; D004298:Dopamine