Intracerebroventricular infusion of dopamine and its agonists in rodents and primates. An experimental approach to the treatment of Parkinson's disease.
The authors investigated the effects of chronic intracerebroventricular (ICV) infusion of dopamine (DA) and DA agonists in animal models of DA deficiency in rodents and primates. Rats with unilateral nigrostriatal lesions induced by 6-OH-DA received infusions of DA, pergolide, lisuride, and (+)-4-propyl-9-hydroxynaphthoxacine (PHNO) for from 1 to 2 weeks through a catheter implanted into the cerebral ventricle ipsilateral to the lesion and connected to an osmotic minipump filled with the active substance. The infused animals had persistent contralateral rotation during the period of infusion. The DA infusion restored DA levels in lesioned animals. In animals treated chronically with reserpine, the ICV DA infusion restored DA levels in the brain, but akinesia was not reversed unless monoamine oxidase inhibiters were also given, intraperitoneally or ICV, with the DA infusion. An ICV infusion of PHNO reversed reserpine-induced akinesia. The infusion of DA or PHNO restored normal patterns of behavior in monkeys made akinetic by treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), but the infusion was complicated by intolerance to the pump or frequent disconnection of the catheter. An ICV infusion of PHNO may be an alternative experimental approach to the treatment of fluctuations in patients with Parkinson's disease.
Garcia de Yebenes
J
J
Centro Ramon y Cajal, Madrid, Spain.
Fahn
S
S
Mena
M A
MA
Pardo
B
B
Casarejos
M J
MJ
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D004195:Disease Models, Animal; D004298:Dopamine / Q000008:administration & dosage*; D015259:Dopamine Agents / Q000008:administration & dosage*; D006892:Hydroxydopamines; D007276:Injections, Intraventricular; D008252:Macaca fascicularis; D009043:Motor Activity / Q000187:drug effects; D010078:Oxazines / Q000008:administration & dosage; D016627:Oxidopamine; D010300:Parkinson Disease / Q000188:drug therapy*; D011725:Pyridines; D051381:Rats; D012110:Reserpine
D015259:Dopamine Agents; D006892:Hydroxydopamines; D010078:Oxazines; D011725:Pyridines; C042631:naxagolide; D012110:Reserpine; D016627:Oxidopamine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine