Linked Life Data

9628768

Source:http://linkedlifedata.com/resource/pubmed/id/9628768

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1998-7-9
pubmed:abstractText
Long-term treatment of Parkinson's disease with dopamine-replacing agents such as L-3,4-dihydroxyphenylalanine (L-DOPA) is compromised by many side-effects, most notably involuntary movements, L-DOPA-induced dyskinesia. Acute challenge with dopamine-replacing drugs elicits a rotational response in the 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease. This rotation is contraversive to the lesion and is considered to represent an antiparkinsonian effect. More recently, it has become clear that the rotational response shows plasticity and that repeated L-DOPA or apomorphine therapy is accompanied by a marked enhancement in this response. In this study, we demonstrate that the enhanced behavioral response to repeated dopamine-replacement therapy seen in the 6-OHDA-lesioned rat has pharmacological characteristics similar to L-DOPA-induced dyskinesia seen in MPTP-lesioned primates and man. Thus, the magnitude and rate of development of the enhanced response to L-DOPA treatment is related to both the number of doses and the size of the dose of L-DOPA administered. In contrast, de novo administration of dopaminergic drugs that are associated with a lower incidence of dyskinesia, e.g., bromocriptine or lisuride, does not lead to an enhanced behavioral response following repeated treatment. However, following a single "priming" administration of apomorphine, the rotational response elicited by subsequent bromocriptine administrations is enhanced with repeated treatment. Once established, the enhanced behavioral response to repeated L-DOPA-administration (6.5 mg/kg, twice daily) can, like L-DOPA-induced dyskinesia in man and MPTP-treated monkeys, be selectively reduced by coadministration of L-DOPA with the alpha2-adrenergic receptor antagonist yohimbine (10 mg/kg, -95%), the 5-HT uptake inhibitor 5-MDOT (2 mg/kg, -90%), or the beta-adrenergic receptor antagonist propranalol (10 mg/kg, -35%). While these rats do not exhibit symptoms of dyskinesia per se, this rodent model does exhibit behaviors, the underlying mechanism of which is likely to be similar to that underlying L-DOPA-induced dyskinesia and may prove useful in studying the molecular and cellular mechanisms of L-DOPA-induced dyskinesia in Parkinson's disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic alpha-Agonists, http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic alpha-Antagonists, http://linkedlifedata.com/resource/pubmed/chemical/Antiparkinson Agents, http://linkedlifedata.com/resource/pubmed/chemical/Bromocriptine, http://linkedlifedata.com/resource/pubmed/chemical/Clonidine, http://linkedlifedata.com/resource/pubmed/chemical/Dopamine Uptake Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Levodopa, http://linkedlifedata.com/resource/pubmed/chemical/Lisuride, http://linkedlifedata.com/resource/pubmed/chemical/Mazindol, http://linkedlifedata.com/resource/pubmed/chemical/Methoxydimethyltryptamines, http://linkedlifedata.com/resource/pubmed/chemical/Oxidopamine, http://linkedlifedata.com/resource/pubmed/chemical/Sympatholytics, http://linkedlifedata.com/resource/pubmed/chemical/Tritium, http://linkedlifedata.com/resource/pubmed/chemical/Yohimbine
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0014-4886
pubmed:author
pubmed:copyrightInfo
Copyright 1998 Academic Press.
pubmed:issnType
Print
pubmed:volume
151
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
334-42
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:9628768-Adrenergic alpha-Agonists, pubmed-meshheading:9628768-Adrenergic alpha-Antagonists, pubmed-meshheading:9628768-Animals, pubmed-meshheading:9628768-Antiparkinson Agents, pubmed-meshheading:9628768-Behavior, Animal, pubmed-meshheading:9628768-Bromocriptine, pubmed-meshheading:9628768-Clonidine, pubmed-meshheading:9628768-Disease Models, Animal, pubmed-meshheading:9628768-Dopamine, pubmed-meshheading:9628768-Dopamine Uptake Inhibitors, pubmed-meshheading:9628768-Dyskinesia, Drug-Induced, pubmed-meshheading:9628768-Levodopa, pubmed-meshheading:9628768-Lisuride, pubmed-meshheading:9628768-Locomotion, pubmed-meshheading:9628768-Male, pubmed-meshheading:9628768-Mazindol, pubmed-meshheading:9628768-Methoxydimethyltryptamines, pubmed-meshheading:9628768-Oxidopamine, pubmed-meshheading:9628768-Parkinson Disease, Secondary, pubmed-meshheading:9628768-Prosencephalon, pubmed-meshheading:9628768-Rats, pubmed-meshheading:9628768-Rats, Sprague-Dawley, pubmed-meshheading:9628768-Sympatholytics, pubmed-meshheading:9628768-Tritium, pubmed-meshheading:9628768-Yohimbine
pubmed:year
1998
pubmed:articleTitle
Characterization of enhanced behavioral responses to L-DOPA following repeated administration in the 6-hydroxydopamine-lesioned rat model of Parkinson's disease.
pubmed:affiliation
Division of Neuroscience, School of Biological Sciences, University of Manchester, 1.124 Stopford Building, Manchester, M13 9PT, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't