Publication Date:
1996-08-02
Description:
Chronic morphine administration induces an up-regulation of several components of the cyclic adenosine 5'-monophosphate (cAMP) signal transduction cascade. The behavioral and biochemical consequences of opiate withdrawal were investigated in mice with a genetic disruption of the alpha and Delta isoforms of the cAMP-responsive element-binding protein (CREB). In CREBalphadelta mutant mice the main symptoms of morphine withdrawal were strongly attenuated. No change in opioid binding sites or in morphine-induced analgesia was observed in these mutant mice, and the increase of adenylyl cyclase activity and immediate early gene expression after morphine withdrawal was normal. Thus, CREB-dependent gene transcription is a factor in the onset of behavioral manifestations of opiate dependence.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maldonado, R -- Blendy, J A -- Tzavara, E -- Gass, P -- Roques, B P -- Hanoune, J -- Schutz, G -- New York, N.Y. -- Science. 1996 Aug 2;273(5275):657-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departement de Pharmacochimie Moleculaire et Structurale, Unite de Recherche Associee D1500 CNRS, Universite Rene Descartes, Faculte de Pharmacie, Paris, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8662559" target="_blank"〉PubMed〈/a〉
Keywords:
Adenylyl Cyclases/metabolism
;
Analgesia
;
Animals
;
Behavior, Animal
;
Cerebral Cortex/enzymology
;
Cyclic AMP Response Element-Binding Protein/*genetics/*physiology
;
Drug Tolerance
;
Gene Expression Regulation
;
Gene Targeting
;
Genes, Immediate-Early
;
Locus Coeruleus/metabolism
;
Mice
;
Morphine/*administration & dosage/adverse effects/pharmacology
;
Morphine Dependence/*etiology/metabolism
;
Mutation
;
Naloxone/pharmacology
;
Receptors, Opioid/metabolism
;
Signal Transduction
;
Substance Withdrawal Syndrome/*physiopathology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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