Reduction of Morphine Abstinence in Mice with a Mutation in the Gene Encoding CREB

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Science  02 Aug 1996:
Vol. 273, Issue 5275, pp. 657-659
DOI: 10.1126/science.273.5275.657


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 α and Δ isoforms of the cAMP-responsive element-binding protein (CREB). In CREBαΔ 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.

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