Linked Life Data

14975676

Source:http://linkedlifedata.com/resource/pubmed/id/14975676

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-2-20
pubmed:abstractText
Opiate addiction is associated with abnormalities of neurofilament (NF) proteins and upregulation of cAMP signaling in the brain, which may modulate neuronal plasticity. This study investigated, using gene-targeted mice lacking mu-, delta- or kappa-opioid receptors, the role of these receptors in modulating the basal activity and the chronic effects of morphine on both intracellular targets. In WT mice, chronic treatment (5 days) with morphine (20-100 mg/kg) resulted in decreases in the immunodensity of neurofilament (NF)-L in the cerebral cortex (14-23%). In contrast, chronic morphine did not decrease NF-L in cortices of mu-, delta-, and kappa-KO mice, suggesting the involvement of the three types of opioid receptors in this effect of morphine. Also, the marked increase in phosphorylated NF-H induced by chronic morphine in WT mice (two-fold) was abolished in mu -KO mice. In cortex and/or striatum of mu-, delta- and kappa-KO mice, the basal immunodensities of Galphai1/2 proteins, the catalytic isoform (Calpha) of protein kinase A (PKA) and the total content of cAMP response element-binding protein (CREB, the nuclear target of PKA) were not different from those of WT mice. In contrast, phosphorylated CREB (the active form of this transcription factor) was reduced in cortex and/or striatum (23-26%) of mu- and delta-KO mice, but not in kappa-KO animals. These results suggest that the endogenous opioid tone acting on mu-/delta-receptors tonically stimulate CREB activation in the brain. In cortex and/or striatum of WT mice, chronic morphine did not induce upregulation of the main components of the cAMP signaling pathway. In contrast, chronic morphine treatment in mu-KO mice, but not in delta- or kappa-KO, resulted in a paradoxical upregulation of Galphai1/2 (12-19%), PKA (19-21%,) and phosphorylated CREB (21-73%), but not total CREB, in cortex and/or striatum. The induction of heterologous receptor adaptations in mu-KO mice may explain this paradoxical effect of morphine.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0028-3908
pubmed:author
pubmed:issnType
Print
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
519-30
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Neurofilament proteins and cAMP pathway in brains of mu-, delta- or kappa-opioid receptor gene knock-out mice: effects of chronic morphine administration.
pubmed:affiliation
Laboratori de Neurofarmacologia, Unitat Associada de l'Instituto de Neurobiología "Ramón y Cajal" (CSIC), Facultat de Ciències, Universitat de les Illes Balears, E-07122 Palma de Mallorca, Spain. jesus.a.garcia-sevilla@hcuge.ch
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't