Continuous intracerebroventricular infusion of dopamine and dopamine agonists through a totally implanted drug delivery system in animal models of Parkinson's disease.
We studied the effect of intracerebroventricular infusion of dopamine and dopamine agonists in rat and primate models of Parkinson's disease as an experimental approach to the treatment of levodopa-induced fluctuations. The infusion of dopamine, lisuride, and pergolide into the ventricle ipsilateral to the lesion, by 6-hydroxydopamine, of the nigrostriatal pathway induced a contralateral rotation which was maximal 24-48 h after infusion and whose intensity progressively decreased over the period of 1 week. [3H]Spiperone binding was decreased by the infusion of dopamine but the responses to subcutaneous apomomorphine were unchanged. The infusion of dopamine also restored the levels of monoamines in the rat brain. In chronic reserpized rats, the infusion of dopamine restored brain levels of dopamine but did not reverse akinesia unless monoamine oxidase inhibitors were simultaneously administered, either systemically or intracerebroventricularly. Lisuride and pergolide proved much weaker than dopamine in reversing the effects of reserpine. Intracerebroventricular infusion of dopamine plus deprenyl reversed MPTP induced akinesia in monkeys but the pump used for the delivery was not well tolerated, because of its size, by the animals.
de Yebenes
J G
JG
Department of Neurology, Columbia University College of Physicians & Surgeons, New York, NY.
Fahn
S
S
Lovelle
S
S
Jackson-Lewis
V
V
Jorge
P
P
Mena
M A
MA
Reiriz
J
J
Bustos
J C
JC
Magariños
C
C
Martinez
A
A
D000818:Animals; D001921:Brain / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects; D004298:Dopamine / Q000008:administration & dosage* / Q000378:metabolism; D015259:Dopamine Agents / Q000008:administration & dosage*; D007260:Infusion Pumps; D007276:Injections, Intraventricular / Q000295:instrumentation*; D008090:Lisuride / Q000008:administration & dosage; D008252:Macaca fascicularis; D008297:Male; D009434:Neural Pathways / Q000187:drug effects; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy*; D010479:Pergolide / Q000008:administration & dosage; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects; D012642:Selegiline / Q000008:administration & dosage; D013239:Stereotyped Behavior / Q000187:drug effects; D013378:Substantia Nigra / Q000187:drug effects
D015259:Dopamine Agents; D011954:Receptors, Dopamine; D010479:Pergolide; D012642:Selegiline; D008090:Lisuride; D004298:Dopamine