Linked Life Data

9758230

Source:http://linkedlifedata.com/resource/pubmed/id/9758230

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1998-12-3
pubmed:abstractText
The pathophysiologic basis of tardive dyskinesia remains unclear. It has been proposed that tardive dyskinesia may be a result of excitotoxic neurodegeneration in the striatum caused by a neuroleptic-induced increase in striatal glutamate release and impaired energy metabolism. To investigate this hypothesis, haloperidol decanoate (38 mg/kg/four weeks intramuscularly) and the succinate dehydrogenase inhibitor 3-nitropropionic acid (8 mg/kg/day via subcutaneous osmotic mini-pumps), were administered alone or together for 16 weeks to four-months-old rats. Control rats received sesame oil intramuscularly and had empty plastic tubes subcutaneously. Vacuous chewing movements, a putative analogue to human tardive dyskinesia, were recorded during and after drug treatment. Haloperidol alone, 3-nitropropionic acid alone, and 3-nitropropionic acid+haloperidol treatments induced an increase in vacuous chewing movements. However, vacuous chewing movements were more pronounced and appeared earlier in rats treated with 3-nitropropionic acid+haloperidol. After drug withdrawal, increases in vacuous chewing movements persisted for 16 weeks in the haloperidol alone and 3-nitropropionic acid+haloperidol group and for four weeks in the 3-nitropropionic acid alone group. Brains from each group were analysed for histopathological alterations. Bilateral striatal lesions were present only in rats with high levels of vacuous chewing movements in the 3-nitropropionic acid+haloperidol-treated rats. Nerve cell depletion and astrogliosis were prominent histopathologic features. There was selective neuronal sparing of both large- and medium-sized aspiny striatal neurons. These results suggest that mild mitochondrial impairment in combination with neuroleptics results in striatal excitotoxic neurodegeneration which may underlie the development of persistent vacuous chewing movements in rats and possibly irreversible tardive dyskinesia in humans.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0306-4522
pubmed:author
pubmed:issnType
Print
pubmed:volume
87
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
639-48
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:9758230-Analysis of Variance, pubmed-meshheading:9758230-Animals, pubmed-meshheading:9758230-Anti-Dyskinesia Agents, pubmed-meshheading:9758230-Antihypertensive Agents, pubmed-meshheading:9758230-Behavior, Animal, pubmed-meshheading:9758230-Corpus Striatum, pubmed-meshheading:9758230-Dyskinesia, Drug-Induced, pubmed-meshheading:9758230-Female, pubmed-meshheading:9758230-Glial Fibrillary Acidic Protein, pubmed-meshheading:9758230-Haloperidol, pubmed-meshheading:9758230-Mastication, pubmed-meshheading:9758230-Mouth, pubmed-meshheading:9758230-NADPH Dehydrogenase, pubmed-meshheading:9758230-Nerve Degeneration, pubmed-meshheading:9758230-Neuroglia, pubmed-meshheading:9758230-Neurons, pubmed-meshheading:9758230-Nitro Compounds, pubmed-meshheading:9758230-Propionic Acids, pubmed-meshheading:9758230-Rats, pubmed-meshheading:9758230-Rats, Sprague-Dawley, pubmed-meshheading:9758230-Tyrosine 3-Monooxygenase
pubmed:year
1998
pubmed:articleTitle
Oral Dyskinesias and striatal lesions in rats after long-term co-treatment with haloperidol and 3-nitropropionic acid.
pubmed:affiliation
Department of Physiology, Sandviken Hospital, University of Bergen, Norway.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't