A 6-hydroxydopamine-induced selective parkinsonian rat model: further biochemical and behavioral characterization.
The main focus of the present study was to define the rotational response of 6-hydroxydopamine-lesioned rats to dopaminergic agonists to separate the partially lesioned rats from those having complete substantia nigra (SN) and ventral tegmental area (VTA) lesions. Animals were challenged by amphetamine and L-DOPA for 10 consecutive weeks. There was a correlation between rotational behavior and extent of midbrain cell loss. Rats with complete SN and < 40% VTA lesion turned more than 5 times/min after amphetamine administration, but not after L-DOPA; animals with complete SN and 40-80% VTA lesions turned vigorously following amphetamine and began turning after L-DOPA administration. Rats with complete SN and VTA lesions turned less after amphetamine than the other two groups, while their turning after L-DOPA administration increased. Extracellular dopamine (DA) measured by microdialysis, intracellular DA measured by postmortem tissue punches, and tyrosine hydroxylase-immunoreactive cell count in SN and VTA were also evaluated. It appears that the dopaminergic cells in the lateral VTA affect DA concentration in the medial caudate nucleus. In the nucleus accumbens of the lesioned side, DA release and metabolism substantially increased with the larger VTA lesion. Dopamine turnover rate in the caudate was also higher in the group with < 40% VTA lesion.
Thomas
J
J
CNS Implantation & Regeneration Unit, NINDS, National Institutes of Health, Bethesda, Maryland 20892.
Wang
J
J
Takubo
H
H
Sheng
J
J
de Jesus
S
S
Bankiewicz
K S
KS
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002230:Carbidopa / Q000494:pharmacology*; D002421:Caudate Nucleus / Q000378:metabolism; D003342:Corpus Striatum / Q000201:enzymology / Q000473:pathology; D004298:Dopamine / Q000378:metabolism*; D004338:Drug Combinations; D007839:Functional Laterality; D007150:Immunohistochemistry; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D008636:Mesencephalon / Q000201:enzymology / Q000473:pathology; D008959:Models, Neurological; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009714:Nucleus Accumbens / Q000378:metabolism; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012399:Rotation; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis / Q000378:metabolism
D004338:Drug Combinations; C009265:carbidopa, levodopa drug combination; D007980:Levodopa; D016627:Oxidopamine; D000661:Amphetamine; D014446:Tyrosine 3-Monooxygenase; D002230:Carbidopa; D004298:Dopamine