Linked Life Data

17988775

Source:http://linkedlifedata.com/resource/pubmed/id/17988775

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-2-5
pubmed:abstractText
GABAergic hypofunction in the basal ganglia is stated as an important mechanism underlying the pathophysiology of tardive dyskinesia. In the present study we sought to establish the protective effect of progesterone in haloperidol-induced orofacial dyskinesia. Besides this we also tried to find out whether the GABA(A) facilitatory action of progesterone metabolites is responsible for the action of progesterone in attenuating the haloperidol-induced orofacial dyskinesia, an animal model of tardive dyskinesia. Chronic administration of haloperidol (1 mg/kg, i.p. 21 days) induced significant increase in hyperkinetic orofacial dyskinetic movements and oxidative damage in the brain as compared to control group. Coadministration of progesterone (5-20 mg/kg, i.p. 21 days) dose dependently prevented the hyperkinetic orofacial movements as well as oxidative damage parameters. The protective activity of progesterone was reversed by pre treatment with finasteride (50 mg/kg i.p.), a 5alpha-reductase inhibitor that blocks the metabolism of progesterone to allopregnanolone and other metabolites. Further, chronic administration of haloperidol resulted in significant decrease in dopamine levels in rat striatum homogenates and increase in catecholamine metabolite levels. Coadministration of progesterone also reversed the decrease in dopamine levels induced by chronic haloperidol treatment, an effect which was again reversed by pre treatment with finasteride. Our study provides strong evidence that the protective effect of progesterone resides in the GABAergic as well as neuroprotective activity of its metabolite allopregnanolone. These findings lend support to recognized GABA hypofunction theory of tardive dyskinesia and strongly suggest progesterone as a protective therapy in this debilitating movement disorder.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0278-5846
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
32
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
451-61
pubmed:meshHeading
pubmed-meshheading:17988775-Animals, pubmed-meshheading:17988775-Antipsychotic Agents, pubmed-meshheading:17988775-Brain Diseases, pubmed-meshheading:17988775-Control Groups, pubmed-meshheading:17988775-Disease Models, Animal, pubmed-meshheading:17988775-Dopamine, pubmed-meshheading:17988775-Dyskinesia, Drug-Induced, pubmed-meshheading:17988775-Haloperidol, pubmed-meshheading:17988775-Male, pubmed-meshheading:17988775-Movement Disorders, pubmed-meshheading:17988775-Neuroprotective Agents, pubmed-meshheading:17988775-Oxidative Stress, pubmed-meshheading:17988775-Pregnanolone, pubmed-meshheading:17988775-Progesterone, pubmed-meshheading:17988775-Rats, pubmed-meshheading:17988775-Rats, Inbred ACI, pubmed-meshheading:17988775-Receptors, GABA-A, pubmed-meshheading:17988775-gamma-Aminobutyric Acid
pubmed:year
2008
pubmed:articleTitle
Progesterone attenuates neuroleptic-induced orofacial dyskinesia via the activity of its metabolite, allopregnanolone, a positive GABA(A) modulating neurosteroid.
pubmed:affiliation
Centre with Potential for Excellence in Biomedical Sciences (CPEBS), Panjab University, Chandigarh 160014, India.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't