Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protracted long-term treatment of common marmosets with 15 doses (0.5-4.5 mg/kg, i.p.) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; total dose 25 mg/kg, given over 29 days) caused transitory changes in motor behaviour reminiscent of human Parkinson's disease. 16 days from the start of MPTP administration, all animals showed motor impairment, consisting of profound akinesia and a rigid posture, but in no case resting tremor. Biogenic amines were measured in nigrostriatal regions one month after finishing MPTP treatment. There was a profound loss of dopamine and serotonin in the substantia nigra and in the striatum; noradrenaline was only reduced in the putamen. Continuous analyses of the concentrations of biogenic amine metabolites in the CSF during this study revealed persistent dopaminergic disturbances and temporary alterations in serotoninergic and noradrenergic function.
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PMID:Neurochemical and behavioural features induced by chronic low dose treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the common marmoset: implications for Parkinson's disease? 171 88

We assessed clinical and electrophysiologic characteristics of tremor in patients with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Four of seven patients with moderate to severe MPTP-induced parkinsonism exhibited a tremor indistinguishable from the characteristic rest tremor of Parkinson's disease (PD). The pathology induced by MPTP in one human case is confined to the substantia nigra, but in nonhuman primates, the locus ceruleus or the ventral tegmental area can also be affected. These findings suggest that the pathophysiology of rest tremor in PD might result from damage to either the substantia nigra alone or in combination with damage to one or more of these other regions.
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PMID:Tremor in MPTP-induced parkinsonism. 843 27

To study MPTP-induced muscular rigidity, we try to detect the changes of both dopamine (DA) and GABA within rat striatums by immunohistochemical means. A high dose (30 mg/kg) of MPTP i.p. injected into rats produces behavioral abnormalities (tremor and ataxia), and higher doses (greater than 60 mg/kg) develop an acutely muscular rigidity without producing a measurable histological change. GABA is induced in the striatum of 4 MPTP (30 mg/kg) i.p. treated-rats developed tremor and ataxia. But the animals recovered to an apparently normal state and are not showed GABA-immunoreactivity. Dense GABA-immunoreactivity is observed in the striatum developed muscular rigidity, when the animals are injected with 60 mg/kg MPTP i.p.. At this time, their striatums show slight decrease of DA-immunoreactivity in medium sized-spiny neurons. The results give some insight as to how DA and GABA function within the striatum with respect to the development of neuronal abnormalities. It is also suggested by our behavioral and immunohistochemical studies that effects induced by the depletion of DA within the striatum may be mediated through the inhibition of the striato-nigral GABAergic pathway, which in turn may lead to an activation of the nigrothalamic or nigro-collicular GABAergic pathway. This study indicates that the role of striatal GABAergic transmission is important in the development of muscular rigidity. The activity within the striatum can be followed with immunohistochemical technique for GABA morphologically.
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PMID:Immunohistochemical detection of GABA in rat striatum by intraperitoneal injection of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). 180 45

Systemic administration of the selective D1 antagonist, SCH 23390, caused significant motor changes in healthy African green monkeys. The effects included the parkinsonian signs of motor freezing, incoordination, bradykinesia, poverty of movement, tremor and depressed blink rate. SCH 23390 administered to MPTP-treated monkeys increased existing parkinsonism. The results are of particular interest in light of recent data that demonstrate the effectiveness of dihydrexidine, a full D1 agonist, in alleviating parkinsonism in MPTP-treated monkeys. These data implicate D1 receptors in the functions impaired by Parkinson's disease and suggest the possibility of parkinsonian side effects in the clinical use of this or similar D1 antagonists as treatments for psychiatric disorders.
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PMID:The D1 receptor antagonist, SCH 23390, induces signs of parkinsonism in African green monkeys. 183 30

Six pairs of female squirrel monkeys were given a daily intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 9-14 days, beginning the same day on which they received either a bilateral 6-hydroxydopamine lesion or a sham lesion of the locus coeruleus. Sham animals developed typical parkinsonian signs (i.e. tremor, bradykinesia, hypokinesia and reduced blink rate) which largely recovered by six to nine weeks after the start of MPTP treatment. At nine weeks, post mortem levels of striatal dopamine in these same animals were partially reduced (by 45%), and this only in the putamen, compared to values obtained from three non-operated, normal control animals. Additionally, histological examination revealed a moderate loss of neuronal cell bodies in the substantia nigra, pars compacta. In marked contrast, the locus coeruleus-lesioned monkeys exhibited little or no recovery from the parkinsonian signs induced by MPTP. Post mortem examination of these animals revealed profound decreases in caudate (by 84%) and putamen (by 91%) dopamine content, and severe neuronal cell loss in the substantia nigra pars compacta of all animals. These neurological, biochemical and histological assessments indicate that lesioning of the locus coeruleus impairs the recovery which usually occurs from the parkinsonian manifestations induced by MPTP in squirrel monkeys. The results support the hypothesis that deficient locus coeruleus noradrenergic mechanisms underlie the progression of Parkinson's disease.
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PMID:Effects of locus coeruleus lesions on parkinsonian signs, striatal dopamine and substantia nigra cell loss after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in monkeys: a possible role for the locus coeruleus in the progression of Parkinson's disease. 187 Jul 1

Fetal substantia nigra (SN) cells were transplanted into the caudate nucleus (CN) of four vervet monkeys (Cercopithecus aethiops sabaeus) that had been treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP treatment appears to produce a syndrome similar to that observed in patients with idiopathic Parkinson's disease. Normal and parkinsonian behaviors were quantitated by trained observers 5 days/week. Twenty-eight behaviors based on previous factor analyses were individually scored and rated. Parkinsonian signs included freezing, head and limb tremor, difficulty in eating, delayed initiation of movement, poverty of movement, tremor that stopped with intention, decreased response to threats, and lying immobile in the cage. These signs were combined to give an overall rating of parkinsonism. A summary measure of 'normal' healthy behavior was also examined, including such behaviors as yawning, scratching, self-grooming, shifting, and eating. Overall ratings of parkinsonism increased and those of healthy behavior decreased after MPTP. In the 4 monkeys grafted with fetal SN cells into the CN, behavior returned to pre-treatment levels by the time of sacrifice (2, 5, or 7.5 months after grafting). Three control subjects were transplanted with either SN cells into an inappropriate brain site (cortex) or inappropriate, non-dopaminergic, cells (cerebellar) into the CN. Subjects were also compared with three control animals that did not receive MPTP but received cryopreserved or fresh SN and other cells into the CN. Only MPTP-treated subjects that received SN cells into the CN showed evidence of a reversal of the MPTP syndrome after transplantation. In addition, grafting in animals that were not MPTP-treated did not appear to affect behavior. This paper reports the specific behavioral effects of severe MPTP toxicity that were or were not reversed after transplantation and suggests that only fetal SN cells grafted into the CN may be able to reverse behavioral deficits in MPTP-treated monkeys.
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PMID:Grafting of fetal substantia nigra to striatum reverses behavioral deficits induced by MPTP in primates: a comparison with other types of grafts as controls. 189 83

The purported alpha 2-adrenergic agonist clonidine was found to inhibit rest tremor at doses of 0.023-0.1 mg/kg in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine monkey model of parkinsonism. The effect was dose dependent, but sedation and reduced mobility were observed. Atropine at doses of 0.1-1 mg/kg also reduced tremor in a dose-dependent fashion, but side-effects in the form of agitation, dilated pupils, and dry mouth were seen. When the two drugs were combined, however, we saw a significant potentiation of the antitremor effect. We could even abolish tremor with doses of atropine and clonidine that by themselves were without effect. The side-effects were almost eliminated by the combination.
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PMID:Effect of clonidine and atropine on rest tremor in the MPTP monkey model of parkinsonism. 191 2

After local surgical exposure, we administrated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) directly into the right common carotid artery of 5 rhesus monkeys. All the monkeys manifested akinesia, rigidity and postural tremor of the contralateral limbs, and spontaneous circling toward the MPTP treated side. These disturbances began to appear 3-4 days after injection, peaking at one month, and continued until the day of sacrifice. After treatment with madopar and apomorphine, marked improvements of the motor impairments appeared and a striking reversal of the direction of rotation away from the MPTP-treated side occurred in a dose-dependent manner. The ipsilateral neurotoxicity was confirmed biochemically by 99% reduction in the caudate-putamen dopamine levels and histologically by selective cell loss in the substantia nigra of the MPTP-treated side. It is concluded that this primate model of hemiparkinsonism is easy to reproduce and life is maintained with good health otherwise. So it may be more feasible for behavioral and pharmacological studies of Parkinson's disease.
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PMID:Hemiparkinsonism in monkeys following unilateral common carotid artery infusion of MPTP. A study of behavior, biochemistry and histology. 193 58

Parkinson's disease (PD) is a common neurodegenerative disease of old age characterized by triad of akinesia, rigidity and tremor, reduction of dopamine (DA) content in the nigrostriatum, and severe degeneration of neuron in the substantia nigra. The significant changes after the use of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to rhesus monkeys and C57 black mice are (a) serotonin-like reactions and Parkinsonian symptoms in monkeys and "stickclimbing" disturbance in mice; (b) marked DA reduction in substantia nigra (72.5%), putamen (93.3%), caudate nucleus (91.2%) of monkeys and striatum (94%) of mice; (c) reduction of Met-enkephalin (75%) and Leu-enkephalin (66%) in mouse striatum; and (d) severe degeneration of neurons in the substantia nigra of monkeys and mice. The results suggest that MPTP-treated monkey and C57 black mouse provides useful Parkinsonian animal models and produces behavioral, biochemical and histopathological changes similar to those of human PD.
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PMID:[Experimental research on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonian animal models in the rhesus monkey and C57 black mouse]. 216 92

The selective dopaminergic antagonist ligands [3H]SCH 23390 and [3H]sulpiride were used to reveal autoradiographically dopamine D1 and D2 receptors, respectively, in brain sections from monkeys which had received unilateral intracarotid infusions of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), causing loss of dopamine-containing neurones of the substantia nigra pars compacta. The monkeys developed hemi-parkinsonian symptoms (tremor, bradykinesia) in limbs contralateral to the side of the toxin infusion. Administration of apomorphine (0.05-0.25 mg/kg) caused contralateral rotational behaviour, and reversal of the parkinsonian symptoms. Loss of forebrain dopaminergic terminals was assessed autoradiographically using [3H]mazindol to label dopamine uptake sites. A reduction in these sites of 97% (mean brain value) in the caudate nucleus, and 91% in the putamen, as compared with binding values from untreated control monkeys, was accompanied by a significant increase in the binding of [3H]sulpiride (D2) in these structures. In contrast, in the same animals there was no similar increase in [3H]SCH 23390 binding to D1 receptors in the denervated areas. These results suggest that in the parkinsonian brain, where the dopaminergic innervation of the caudate nucleus and putamen has been lost, D2 receptors may be more susceptible than D1 receptors to changes, revealed here as an increase in [3H]sulpiride binding sites.
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PMID:Autoradiographic studies in animal models of hemi-parkinsonism reveal dopamine D2 but not D1 receptor supersensitivity. II. Unilateral intra-carotid infusion of MPTP in the monkey (Macaca fascicularis). 219 72


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