First Author | Maldonado R | Year | 1996 |
Journal | Science | Volume | 273 |
Issue | 5275 | Pages | 657-9 |
PubMed ID | 8662559 | Mgi Jnum | J:34605 |
Mgi Id | MGI:82060 | Doi | 10.1126/science.273.5275.657 |
Citation | Maldonado R, et al. (1996) Reduction of morphine abstinence in mice with a mutation in the gene encoding CREB [see comments]. Science 273(5275):657-9 |
abstractText | 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. |