Pramipexole attenuates the dopaminergic cell loss induced by intraventricular 6-hydroxydopamine.
The D3 preferring dopamine agonist pramipexole has been shown to attenuate the cell loss induced by levodopa in vitro. Pramipexole was herein evaluated in the 6-hydroxydopamine lesion model to determine its in vivo effect. Rats were treated with pramipexole or saline before and after an intracerebroventricular 6-hydroxydopamine injection. In the preliminary study, 6-hydroxydopamine produced a 68% reduction in striatal dopamine and a 62% loss in tyrosine hydroxylase immunoreactive (THir) cell counts in the substantia nigra. Pramipexole treated animals exhibited a 29% and a 27% reduction in striatal dopamine and THir cell counts, respectively. THir cell counts and striatal dopamine were significantly correlated. In the stereological study, 6-hydroxydopamine reduced THir cell counts by 47% in saline treated animals and 26% in pramipexole treated animals. These data demonstrate that pramipexole attenuates the biochemical and THir cell changes normally produced by 6-hydroxydopamine consistent with its neuroprotective actions in vitro.
Vu
T Q
TQ
Department of Neurological Sciences, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 60612, USA.
Ling
Z D
ZD
Ma
S Y
SY
Robie
H C
HC
Tong
C W
CW
Chen
E Y
EY
Lipton
J W
JW
Carvey
P M
PM
D000818:Animals; D052160:Benzothiazoles; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects* / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology*; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D000077487:Pramipexole; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D013844:Thiazoles / Q000494:pharmacology*
D052160:Benzothiazoles; D018491:Dopamine Agonists; D018696:Neuroprotective Agents; D013844:Thiazoles; D000077487:Pramipexole; D016627:Oxidopamine; D004298:Dopamine