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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-12-12
pubmed:abstractText
Based largely on in vitro measurements, the mechanism of several antidepressant treatments is thought to involve upregulation of 3'-5'-cyclic adenosine monophosphate (cAMP) signal transduction cascade and a corresponding increase in phosphodiesterase (PDE) 4, the enzyme that metabolizes cAMP. To assess the in vivo status of PDE4, rats were chronically treated with imipramine and then studied with: (1) in vivo positron emission tomography (PET) measurement of (R)-[(11)C]rolipram binding, (2) in vitro measurement of [(3)H]rolipram binding in brain homogenates, and (3) Western blotting for protein levels of PDE4 isoforms. Imipramine administration caused no significant change in B(max)/K(d), for both in vivo measurements with (R)-[(11)C]rolipram and in vitro measurements with [(3)H]rolipram in frontal cortex, hippocampus, and diencephalon. None of 10 isoforms of PDE4A, B, and D measured with immunoblots of frontal cortex and hippocampus showed a significant change. In summary, using relatively large brain regions for both in vivo imaging and in vitro measures of radiolabeled ligand binding and protein levels, chronic imipramine treatment via continuous mini-pump administration caused no significant change in PDE4 levels. Most, but not all, prior in vitro studies have found increased PDE4 levels after antidepressant administration. The current results raise questions about the in vivo effects of antidepressant treatment on PDE4 and on other potentially important experimental factors (e.g., continuous infusion vs. intermittent injection of antidepressant) in large brain areas. However, the results do not deny possibility of changes in discrete areas, which were not studied in the current study applying PET.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0887-4476
pubmed:author
pubmed:copyrightInfo
Published 2006 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:volume
61
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
78-86
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:17117418-3',5'-Cyclic-AMP Phosphodiesterases, pubmed-meshheading:17117418-Animals, pubmed-meshheading:17117418-Antidepressive Agents, pubmed-meshheading:17117418-Blotting, Western, pubmed-meshheading:17117418-Brain, pubmed-meshheading:17117418-Brain Mapping, pubmed-meshheading:17117418-Carbon Isotopes, pubmed-meshheading:17117418-Cyclic Nucleotide Phosphodiesterases, Type 4, pubmed-meshheading:17117418-Image Processing, Computer-Assisted, pubmed-meshheading:17117418-Imipramine, pubmed-meshheading:17117418-Male, pubmed-meshheading:17117418-Phosphodiesterase Inhibitors, pubmed-meshheading:17117418-Positron-Emission Tomography, pubmed-meshheading:17117418-Protein Binding, pubmed-meshheading:17117418-Radioligand Assay, pubmed-meshheading:17117418-Rats, pubmed-meshheading:17117418-Rats, Sprague-Dawley, pubmed-meshheading:17117418-Rolipram, pubmed-meshheading:17117418-Time Factors, pubmed-meshheading:17117418-Tritium
pubmed:year
2007
pubmed:articleTitle
In vivo and in vitro measurement of brain phosphodiesterase 4 in rats after antidepressant administration.
pubmed:affiliation
Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA. masahiro.fujita@nih.gov
pubmed:publicationType
Journal Article, In Vitro, Research Support, N.I.H., Intramural