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The 2-deoxyglucose metabolic mapping technique has been used to investigate the neural mechanisms which underlie the symptoms of Parkinsonism in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine primate model of Parkinson's disease. In six cynomolgus monkeys, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine was either (a) administered intravenously to induce(More)
The technique of intracerebral microdialysis has been employed to examine the extracellular level of gamma-aminobutyric acid (GABA) within the lateral segment of the globus pallidus of two cynomolgus monkeys, before and after the induction of parkinsonism with N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Microdialysis probes were acutely implanted(More)
Intracerebral injections of the broad spectrum excitatory amino acid antagonist kynurenic acid (50 ug) alleviated the symptoms of akinesia, tremor and rigidity in a severely parkinsonian monkey. Unilateral injection of kynurenic acid within the medial pallidal segment produced rotational behaviour away from the side of the injection, and the limbs on the(More)
Injection of an excitatory amino acid antagonist, kynurenic acid, into the medial segment of the globus pallidus of the conscious monkey elicited dyskinesia of the contralateral limbs. In most respects the dyskinesia was indistinguishable from the disorder that is produced by ablation of the subthalamic nucleus, or injection of a GABA antagonist into the(More)
The effects of chronic 'continuous' infusion and 'intermittent' modes of levodopa/carbidopa administration on apomorphine induced circling behaviour, DA uptake sites (labelled with [3H]mazindol) and D1 and D2 DA receptor binding (labelled with [3H]SCH 23390 and [3H]sulpiride, respectively) were investigated in rats with unilateral 6-OHDA lesions of the(More)
The neural mechanisms that mediate dystonia were investigated in a novel experimental primate model of dopamine agonist-induced dystonia. This condition was produced by long-term (15 months) dopamine agonist therapy of a macaque monkey that had been rendered hemiparkinsonian by unilateral infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine into the(More)
MPTP induces parkinsonism in monkeys by destruction of the substantia nigra, pars compacta. It can also damage ventral tegmental dopamine neurones and the noradrenergic locus coeruleus, both of which may be affected in Parkinson's disease. Motor symptoms in MPTP-treated monkeys respond readily to levodopa or dopamine agonist therapy. Administration of(More)
The GABA/benzodiazepine receptor complex in the basal ganglia of primates treated with the neurotoxin n-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been studied by semi-quantitative autoradiography with [3H]flunitrazepam ([3H]FNZ). Systemic treatment with MPTP produced a stable and lasting parkinsonian condition, with pronounced bradykinesia,(More)
The right common carotid artery was surgically exposed under general anaesthesia in 6 cynomolgus monkeys and MPTP (0.5-2.2 mg/kg) directly infused. This produced a hemiparkinsonian syndrome in the contralateral limbs which responded to treatment with both levodopa and apomorphine. These drugs also precipitated dose-dependent contralateral rotation which(More)
The effects of chronic 'continuous' and 'intermittent' L-3,4-dihydroxyphenylalanine treatments on GABA receptor function in the basal ganglia of rats with unilateral 6-hydroxydopamine lesions of the medial forebrain bundle was investigated, by autoradiography with [3H]flunitrazepam. The 6-hydroxydopamine lesion itself, increased [3H]flunitrazepam binding in(More)