Linked Life Data

16675135

Source:http://linkedlifedata.com/resource/pubmed/id/16675135

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-7-3
pubmed:abstractText
gamma-Hydroxybutyrate is a widely used recreational drug. Its abuse has been associated with cognitive impairments and development of tolerance and dependence. However, the neural mechanisms underlying these effects remain unclear. In the present study we investigated the possible cellular signaling mechanisms that might mediate gamma-hydroxybutyrate's action. Acute administration of gamma-hydroxybutyrate (500 mg/kg, i.p.) was found to cause a rapid and long-lasting increase in the phosphorylation level of the cAMP-responsive element-binding protein in mouse (C57/BL6) hippocampus. Pretreatment with the specific GABA(B) receptor antagonist [3-[1-(R)-[(3-cyclohexylmethyl)hydroxyphosphinyl]-2-(S)-hydroxy-propyl]amino]ethyl]-benzoic acid (20 mg/kg, i.p.) prevented the action of gamma-hydroxybutyrate, confirming a GABA(B) receptor-mediated mechanism. In addition, acute gamma-hydroxybutyrate administration induced a significant increase in cytosolic cAMP-dependent protein kinase activity in the hippocampus, and pretreatment with the cAMP-dependent protein kinase inhibitor H-89 could prevent the effect of gamma-hydroxybutyrate on cAMP-responsive element-binding protein phosphorylation, indicating a direct involvement of cAMP-dependent protein kinase in gamma-hydroxybutyrate-induced cAMP-responsive element-binding protein phosphorylation. On the other hand, the increased expression of phosphorylated cAMP-responsive element-binding protein was not observed in the hippocampus of mice subjected to repeated gamma-hydroxybutyrate exposure, suggesting the development of a gamma-hydroxybutyrate-induced desensitization of the signaling pathway leading to cAMP-responsive element-binding protein activation. Since cAMP-responsive element-binding protein activation has been implicated in a variety of neural plasticities, our findings may have revealed a new mechanism underlying gamma-hydroxybutyrate-induced neuroadaptations.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0306-4522
pubmed:author
pubmed:issnType
Print
pubmed:day
11
pubmed:volume
141
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
269-75
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:16675135-Adjuvants, Anesthesia, pubmed-meshheading:16675135-Animals, pubmed-meshheading:16675135-Blotting, Western, pubmed-meshheading:16675135-Cyclic AMP Response Element-Binding Protein, pubmed-meshheading:16675135-Cyclic AMP-Dependent Protein Kinases, pubmed-meshheading:16675135-Drug Interactions, pubmed-meshheading:16675135-Enzyme Activation, pubmed-meshheading:16675135-Enzyme Inhibitors, pubmed-meshheading:16675135-GABA Antagonists, pubmed-meshheading:16675135-Hippocampus, pubmed-meshheading:16675135-Mice, pubmed-meshheading:16675135-Mice, Inbred C57BL, pubmed-meshheading:16675135-Phosphinic Acids, pubmed-meshheading:16675135-Phosphorylation, pubmed-meshheading:16675135-Receptors, GABA-A, pubmed-meshheading:16675135-Sodium Oxybate, pubmed-meshheading:16675135-Time Factors
pubmed:year
2006
pubmed:articleTitle
gamma-Hydroxybutyrate induces cyclic AMP-responsive element-binding protein phosphorylation in mouse hippocampus: an involvement of GABA(B) receptors and cAMP-dependent protein kinase activation.
pubmed:affiliation
Department of Neurology, the David Geffen School of Medicine at UCLA, Neuroscience Research Building, Room 575D, 635 Charles E. Young Drive South, Los Angeles, CA 90095, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural