Linked Life Data

19141300

Source:http://linkedlifedata.com/resource/pubmed/id/19141300

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2009-2-16
pubmed:abstractText
Pharmacotherapy with benzodiazepines is compromised by rapid sedative tolerance and diverse withdrawal symptoms. To assess the role of AMPA-type glutamate receptor GluR-A subunits in neuroadaptation to subchronic benzodiazepine treatment, GluR-A subunit-deficient mice were rendered tolerant by a high-dose seven-day flurazepam treatment (40 mg/kg, s.c., twice a day for 4 days, 60 mg/kg twice a day for 3 days). The acute effects to flurazepam were not changed in the GluR-/- mice compared with their littermate control mice. GluR-A-/- mice developed less tolerance than their controls as demonstrated in behavioral tests for muscle relaxation and sensory functions. Actually, the knockout mice exhibited slower recovery than their littermates from impaired gait and pelvic position after an acute 40 mg/kg dose of flurazepam. The apparent elimination of flurazepam was similarly increased in the knockout and control mice as assessed by blood and brain concentrations 2 h after acute and chronic treatments, but the active metabolite desalkylflurazepam cumulated similarly in both mouse lines. Withdrawal symptoms, precipitated by flumazenil (20 mg/kg, s.c.) 48 h after discontinuation of the flurazepam treatment, were enhanced in the GluR-A-/- mice. The results stress the importance of the AMPA-receptor system in neuroadaptation to acute and chronic effects of benzodiazepines.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0091-3057
pubmed:author
pubmed:issnType
Print
pubmed:volume
92
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
283-90
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Reduced benzodiazepine tolerance, but increased flumazenil-precipitated withdrawal in AMPA-receptor GluR-A subunit-deficient mice.
pubmed:affiliation
Institute of Biomedicine, Pharmacology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't