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Symptomatic and asymptomatic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated primates: biochemical changes in striatal regions.
Elsworth JD, Deutch AY, Redmond DE, Taylor JR, Sladek JR, Roth RH
(1989) Neuroscience 33: 323-31
MeSH Terms: Animals, Cercopithecus, Corpus Striatum, Dopamine, Homovanillic Acid, MPTP Poisoning, Male, Parkinson Disease, Secondary
Show Abstract · Added May 27, 2014
Administration of the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, to primates produces an excellent behavioral model of idiopathic Parkinson's disease. In the vervet monkey, regional biochemical differences in the striatum of two 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated groups were examined one to two months after treatment and compared with controls; one group displayed no observable gross motor abnormalities after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment (asymptomatic), whereas the other group became markedly parkinsonian (symptomatic). In both 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated groups massive depletions of dopamine and homovanillic acid concentrations were observed in the striatum; generally, dopamine losses in the symptomatic group (greater than 95%) were greater than in the asymptomatic group (greater than 75%). However, in striatum, a marked heterogeneity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine susceptibility was found; certain striatal regions having 99% depletion of dopamine even in asymptomatic monkeys. Overall, in ventromedial regions of striatum the losses of dopamine and homovanillic acid concentrations were less than in dorsolateral regions at the same coronal level. There was a significant negative correlation between control homovanillic acid/dopamine ratios and susceptibility of examined regions to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity. Unlike idiopathic, but similar to postencephalitic, Parkinson's disease, dopamine and homovanillic acid levels in caudate nucleus were not spared relative to putamen; in fact, in the asymptomatic group caudate nucleus dopamine and homovanillic acid concentrations were depleted to a greater extent than in putamen.(ABSTRACT TRUNCATED AT 250 WORDS)
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8 MeSH Terms
MPTP-induced parkinsonism: relative changes in dopamine concentration in subregions of substantia nigra, ventral tegmental area and retrorubral field of symptomatic and asymptomatic vervet monkeys.
Elsworth JD, Deutch AY, Redmond DE, Sladek JR, Roth RH
(1990) Brain Res 513: 320-4
MeSH Terms: Animals, Cercopithecus, Dopamine, Homovanillic Acid, MPTP Poisoning, Male, Parkinson Disease, Secondary, Red Nucleus, Substantia Nigra, Tegmentum Mesencephali
Show Abstract · Added May 27, 2014
Dopamine (DA) and homovanillic acid (HVA) concentrations were measured in subregions of substantia nigra, ventral tegmental area and retrorubral field in vervet monkeys 1 to 2 months after treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Identical MPTP treatment regimens produced animals with different degrees of parkinsonism. In asymptomatic monkeys, changes in DA and HVA concentrations in the midbrain DA regions were relatively small and involved central substantia nigra and dorsomedial ventral tegmental area. In contrast, changes in symptomatic monkeys were more severe and widespread, significantly affecting all examined subregions of substantia nigra (greater than 75% DA depletion), both dorsomedial and ventromedial ventral tegmental area and lateral, but not medial, retrorubral field. The data indicate that DA neurons in subregions of substantia nigra, ventral tegmental area and retrorubral field are not equally susceptible to MPTP toxicity. The pattern of MPTP-induced DA and HVA losses in the vervet monkey mesostriatal dopaminergic system may resemble postencephalitic Parkinson's disease more closely than idiopathic Parkinson's disease.
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10 MeSH Terms
Biochemical and behavioral recovery in a rodent model of Parkinson's disease following stereotactic implantation of dopamine-containing liposomes.
During MJ, Freese A, Deutch AY, Kibat PG, Sabel BA, Langer R, Roth RH
(1992) Exp Neurol 115: 193-9
MeSH Terms: Animals, Apomorphine, Corpus Striatum, Delayed-Action Preparations, Dopamine, Drug Carriers, Hydroxydopamines, Liposomes, Male, Parkinson Disease, Secondary, Rats, Rats, Inbred Strains, Stereotaxic Techniques, Stereotyped Behavior, Substantia Nigra
Show Abstract · Added May 27, 2014
We have developed and characterized dopamine-containing liposomes which exhibited in vitro sustained release of dopamine for over 40 days. These liposomes were stereotactically implanted into the partially denervated corpus striatum of rats subjected to unilateral lesions of the substantia nigra. In vivo release of dopamine into striatal extracellular fluid was monitored by microdialysis and behavior was assessed by quantifying apomorphine-induced asymmetric rotation. Extracellular dopamine levels in the partially denervated striatum of the dopamine liposome-treated rats were greater than the levels in the lesioned rats which received control liposomes and these levels remained elevated for 25 days. In parallel, those rats which received dopamine liposomes exhibited partial behavioral recovery, with attenuation of asymmetric rotation following systemic apomorphine administration. These results suggest that dopamine-containing liposomes can partially ameliorate the deficits associated with a rodent model of Parkinson's disease, and demonstrate the potential of this technology as a method for the controlled delivery of therapeutic agents into discrete areas of the brain.
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15 MeSH Terms
Cholinergic stimulation of the caudate nucleus in rats: a model of Parkinson's disease.
Matthews RT, Chiou CY
(1978) Neuropharmacology 17: 879-82
MeSH Terms: Animals, Caudate Nucleus, Choline, Disease Models, Animal, Injections, Male, Parasympathomimetics, Parkinson Disease, Secondary, Rats
Added January 20, 2015
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9 MeSH Terms
Effects of diethylcholine in two animal models of Parkinsonism tremors.
Matthews RT, Chiou CY
(1979) Eur J Pharmacol 56: 159-62
MeSH Terms: Animals, Brain Chemistry, Carbachol, Choline, Disease Models, Animal, Male, Mice, Parkinson Disease, Secondary, Physostigmine, Rats, Trihexyphenidyl
Show Abstract · Added January 20, 2015
(2-Hydroxyethyl) methyldiethylammonium iodide (diethylcholine; DEC) was tested against trihexyphenidyl for its ability to block tremors in two animal models of Parkinsonism tremors. Both DEC (75 mg/kg) and trihexyphenidyl (10 mg/kg) antagonized physostigmine tremors in mice. Both drugs also blocked tremors in rats which received intracaudate injections of carbachol. DEC was more efficacious than trihexyphenidyl in the rat model. No dose-related inhibition of tremors was seen for trihexyphenidyl (5--20 mg/kg) but inhibition by DEC was dose-related (25--50 mg/kg). The ED50 for tremor inhibition in the rat model by DEC was 33 mg/kg. DEC was also shown to cross the blood-brain barrier in mice. The probable mechanism of action of DEC is discussed.
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11 MeSH Terms